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Residency to Reality: The Job Outlook for New Docs
Roshan Bransden didn’t count how many job offers she received during her recently completed training in family medicine. “It was pretty nonstop throughout all of my PGY-3 year,” she said.
Most of the job opportunities were different from the type of position she sought or where she wanted to work. Bransden graduated from residency at Montefiore Hospital in New York and accepted a position as a primary care doctor in Miami, close to where she grew up and where her family lives.
More than half (56%) of all residents in AMN Healthcare’s 2023 Survey of Final-Year Medical Residents received 100 or more job solicitations during their training, the highest figure since the survey began more than 30 years ago, the staffing agency reported.
Employers are recruiting residents earlier, offering residency stipends of $1500 to $2500 up to 18 months before they finish their training if they commit to an employment contract, said Leah Grant, president of AMN Healthcare’s Physician Permanent Solutions division, specializing in doctor recruitment. She said that the company’s clients are already eyeing residents completing their training in 2026.
“The key for residents is not about finding a position but choosing the right one out of many.” Grant added that residents typically aren’t taught negotiation skills or how to evaluate job offers. They tend to choose a position based on location, but they should also consider work–life balance issues such as call schedules and whether incentives such as signing bonuses, relocation allowances, and student loan reimbursement offset the job’s time commitment.
“If you are a physician and you are willing to go anywhere, you will have hundreds of opportunities,” said Tibor Nagy, DO, an emergency medicine fellow who recently searched for jobs. “It depends on what they want out of their careers.”
Location Is a Key Consideration
Nagy said he had fewer options because he was limited by location, staying close to where his wife is finishing her internal medicine residency. He is completing his fellowship at Atrium Health Carolinas Medical Center in Charlotte, North Carolina, and preparing to return to Prisma Health in Greenville, South Carolina, where he did his residency.
He said that the job search was easier than he anticipated considering the tight market following a job report from the American College of Emergency Physicians in 2021 that predicted an oversupply of 8000 emergency medicine physicians by 2030.
Halfway through Nagy’s residency, he sought a fellowship in emergency medical services (EMS) to be more competitive in the job market. After that, “Every door I knocked on was open to hiring. Maybe it’s a regional thing. They were happy to interview me.”
In addition to location, Nagy’s top priorities when choosing a job were stability and being able to use his EMS fellowship to become a medical director of an EMS system, agency, or fire department. He wanted to work for a hospital system with an academic focus without much employee turnover.
Salary vs Benefits
AMN Healthcare received the most physician searches for family medicine doctors, followed by OB/GYNs. The staffing agency reported that close to two thirds (63%) of its search engagements during the 2023-2024 review period were for specialists, reflecting the needs of an aging population.
The highest average starting salaries were for surgical and internal medicine subspecialties, according to AMN Healthcare’s 2024 Physician and Advanced Practitioner Recruiting Incentives. Orthopedic surgery averaged $633,000; urology, $540,000; gastroenterology, $506,000; and pulmonary medicine, $418,000. For comparison, the average starting salaries for primary care doctors were family medicine, $255,000; internal medicine, $255,000; and pediatrics, $233,000.
In addition to starting salaries, many physicians receive signing bonuses, relocation allowances, and continuing medical education (CME) allowances. According to the report, the average signing bonus for physicians was $31,473. The average relocation allowance for physicians was $11,284 and the average CME allowance was $3969.
Salary wasn’t Nagy’s top priority when choosing a job, though he admits that the ability to pay back thousands of dollars in medical school loans will be helpful. Instead of focusing on higher pay to offset student loans, Nagy said he sought nonprofit positions to help him qualify for public service loan forgiveness.
The federal program forgives loan balances after the recipient makes monthly payments for 10 years while working for a government or nonprofit organization. He also racked up 3 years of residency and his fellowship year at nonprofit hospitals toward that commitment.
He said jobs that pay more may require doctors to see more patients. “The hustle may be different. There are definitely tradeoffs,” he said.
Bransden said the position she begins in January will allow her to work part-time with full benefits, among other perks. “My employer is a membership-based practice, so I’ll be able to gift a few memberships to family and friends.”
Going Solo
Mohammad Ibrahim, DO, is among a minority of new physicians who have chosen to set up their own practice.
Only 6% of residents in AMN Healthcare’s 2024 report indicated that a solo practice was among their top two choices, while 20% listed partnering with another physician.
Ibrahim is a sports medicine fellow at the University of Michigan Health-West in Wyoming, after finishing his family medicine residency at Trinity Health Livingston Hospital in Howell, Michigan.
After his fellowship ends, he said he plans to stay in Michigan, where his family lives.
Ibrahim said he began his medical education knowing he wanted to become a solo clinician in private practice. He sees it as a way to have more control over his decisions about patient care and business practices.
Working in a hospital often requires doctors to gain approval from several levels of authority for decisions such as ordering new equipment or forgiving part of a service payment. He also wanted to set his schedule to take Friday afternoons off for Muslim prayer.
Although he realizes the challenges of starting a private practice, Ibrahim said those who go through graduate medical education can figure out how to adapt and overcome any obstacles. “I think it’s more doable than we are led to believe.”
He said that if more residents were exposed to private practice, they might pursue that path. During his training, Ibrahim did a rotation with a private practice physician. “It’s nice to see people proud of what they built, what they contributed.”
Most residents don’t choose private practice. In the AMN Healthcare survey, 68% of residents said that employment by a hospital was among their top two choices for a practice setting, 42% said employment by a single-specialty group, and 32%, employment by a multispecialty group.
Of the majority of job searches AMN Healthcare conducted, 28% were to fill positions in hospital settings, followed by 26% for medical groups, 22% for academic medical centers, 13% for urgent care centers and retail clinics, 6% for solo practices, partnerships, or concierge practice settings, and 5% for Federally Qualified Health Centers/Community Health Centers or Indian Health facilities.
Still, the report noted an increase in recruiting for independent medical practice ownership, which dwindled in recent years, with the majority of doctors today employed likely due to financial obstacles of starting a practice.
The increase in recruiting indicates possible renewed interest in these practice settings, particularly concierge medicine, which allows doctors to avoid the challenges of third-party payments, the report stated.
Grant said that despite the flexibility and financial autonomy of starting their own practice, new providers who choose this path face obstacles, such as competing with urgent care centers and retail health clinics, which have been on the rise in the past year.
Saddled with debt from medical training, most graduating residents will choose to work toward financial stability and then consider their own practice later in their career, she said.
Flexible Schedules
Work schedule/call hours or work-life balance was the biggest factor (36%) guiding residents’ choice of first post-residency positions compared with starting salary (19%), according to the Medscape Resident Salary & Debt Report 2024.
Grant said that larger practices and those closer to rural communities tend to offer more innovative work schedules, especially for certain specialists. Some solo practices that form partnerships could potentially allow flexible schedules such as 4-day work weeks or week-on-week-off arrangements, she added.
Physicians are also opting for the flexibility of temporary, locum tenens work to improve job conditions and address feelings of burnout. Dr. Kaydo, DO, as she’s known on Instagram, posts about her experiences as locum tenens. “I found that I could have more flexibility as a locum. I want to be able to take time off when I want and as long as I wanted,” said the full-time family medicine doctor who practices at an outpatient clinic in Philadelphia.
“Basically, I’m contract-working, and they pay me as much as I work, and I can also take more time off.” Her employer for the past year also allowed her to work 10 hours a day, 4 days a week instead of the more traditional 8-hour, 5-day schedule.
Dr. Kaydo said she believes many young doctors think contract employees don’t have a permanent job, are not guaranteed a certain salary, and could easily lose their jobs. “I’ve found that most places really need doctors and are willing to negotiate.”
She said primary care locum doctors are particularly in demand in rural clinics and urban underserved areas.
Nagy said he is considering being a nocturnist, an emergency medicine doctor who works nights, to have more control over his schedule, higher pay, and more flexible shifts. “I switch days and nights and that can be tiring.”
Bransden said job flexibility was her primary job criterion. “I have a young child, so I wanted to work part-time with the potential for even more flexibility down the line. I am working 3 days a week, 8-hour days with a 1-hour break. A 3-day work week came with a pay cut, but for me, it works and is what I need right now.”
A version of this article appeared on Medscape.com.
Roshan Bransden didn’t count how many job offers she received during her recently completed training in family medicine. “It was pretty nonstop throughout all of my PGY-3 year,” she said.
Most of the job opportunities were different from the type of position she sought or where she wanted to work. Bransden graduated from residency at Montefiore Hospital in New York and accepted a position as a primary care doctor in Miami, close to where she grew up and where her family lives.
More than half (56%) of all residents in AMN Healthcare’s 2023 Survey of Final-Year Medical Residents received 100 or more job solicitations during their training, the highest figure since the survey began more than 30 years ago, the staffing agency reported.
Employers are recruiting residents earlier, offering residency stipends of $1500 to $2500 up to 18 months before they finish their training if they commit to an employment contract, said Leah Grant, president of AMN Healthcare’s Physician Permanent Solutions division, specializing in doctor recruitment. She said that the company’s clients are already eyeing residents completing their training in 2026.
“The key for residents is not about finding a position but choosing the right one out of many.” Grant added that residents typically aren’t taught negotiation skills or how to evaluate job offers. They tend to choose a position based on location, but they should also consider work–life balance issues such as call schedules and whether incentives such as signing bonuses, relocation allowances, and student loan reimbursement offset the job’s time commitment.
“If you are a physician and you are willing to go anywhere, you will have hundreds of opportunities,” said Tibor Nagy, DO, an emergency medicine fellow who recently searched for jobs. “It depends on what they want out of their careers.”
Location Is a Key Consideration
Nagy said he had fewer options because he was limited by location, staying close to where his wife is finishing her internal medicine residency. He is completing his fellowship at Atrium Health Carolinas Medical Center in Charlotte, North Carolina, and preparing to return to Prisma Health in Greenville, South Carolina, where he did his residency.
He said that the job search was easier than he anticipated considering the tight market following a job report from the American College of Emergency Physicians in 2021 that predicted an oversupply of 8000 emergency medicine physicians by 2030.
Halfway through Nagy’s residency, he sought a fellowship in emergency medical services (EMS) to be more competitive in the job market. After that, “Every door I knocked on was open to hiring. Maybe it’s a regional thing. They were happy to interview me.”
In addition to location, Nagy’s top priorities when choosing a job were stability and being able to use his EMS fellowship to become a medical director of an EMS system, agency, or fire department. He wanted to work for a hospital system with an academic focus without much employee turnover.
Salary vs Benefits
AMN Healthcare received the most physician searches for family medicine doctors, followed by OB/GYNs. The staffing agency reported that close to two thirds (63%) of its search engagements during the 2023-2024 review period were for specialists, reflecting the needs of an aging population.
The highest average starting salaries were for surgical and internal medicine subspecialties, according to AMN Healthcare’s 2024 Physician and Advanced Practitioner Recruiting Incentives. Orthopedic surgery averaged $633,000; urology, $540,000; gastroenterology, $506,000; and pulmonary medicine, $418,000. For comparison, the average starting salaries for primary care doctors were family medicine, $255,000; internal medicine, $255,000; and pediatrics, $233,000.
In addition to starting salaries, many physicians receive signing bonuses, relocation allowances, and continuing medical education (CME) allowances. According to the report, the average signing bonus for physicians was $31,473. The average relocation allowance for physicians was $11,284 and the average CME allowance was $3969.
Salary wasn’t Nagy’s top priority when choosing a job, though he admits that the ability to pay back thousands of dollars in medical school loans will be helpful. Instead of focusing on higher pay to offset student loans, Nagy said he sought nonprofit positions to help him qualify for public service loan forgiveness.
The federal program forgives loan balances after the recipient makes monthly payments for 10 years while working for a government or nonprofit organization. He also racked up 3 years of residency and his fellowship year at nonprofit hospitals toward that commitment.
He said jobs that pay more may require doctors to see more patients. “The hustle may be different. There are definitely tradeoffs,” he said.
Bransden said the position she begins in January will allow her to work part-time with full benefits, among other perks. “My employer is a membership-based practice, so I’ll be able to gift a few memberships to family and friends.”
Going Solo
Mohammad Ibrahim, DO, is among a minority of new physicians who have chosen to set up their own practice.
Only 6% of residents in AMN Healthcare’s 2024 report indicated that a solo practice was among their top two choices, while 20% listed partnering with another physician.
Ibrahim is a sports medicine fellow at the University of Michigan Health-West in Wyoming, after finishing his family medicine residency at Trinity Health Livingston Hospital in Howell, Michigan.
After his fellowship ends, he said he plans to stay in Michigan, where his family lives.
Ibrahim said he began his medical education knowing he wanted to become a solo clinician in private practice. He sees it as a way to have more control over his decisions about patient care and business practices.
Working in a hospital often requires doctors to gain approval from several levels of authority for decisions such as ordering new equipment or forgiving part of a service payment. He also wanted to set his schedule to take Friday afternoons off for Muslim prayer.
Although he realizes the challenges of starting a private practice, Ibrahim said those who go through graduate medical education can figure out how to adapt and overcome any obstacles. “I think it’s more doable than we are led to believe.”
He said that if more residents were exposed to private practice, they might pursue that path. During his training, Ibrahim did a rotation with a private practice physician. “It’s nice to see people proud of what they built, what they contributed.”
Most residents don’t choose private practice. In the AMN Healthcare survey, 68% of residents said that employment by a hospital was among their top two choices for a practice setting, 42% said employment by a single-specialty group, and 32%, employment by a multispecialty group.
Of the majority of job searches AMN Healthcare conducted, 28% were to fill positions in hospital settings, followed by 26% for medical groups, 22% for academic medical centers, 13% for urgent care centers and retail clinics, 6% for solo practices, partnerships, or concierge practice settings, and 5% for Federally Qualified Health Centers/Community Health Centers or Indian Health facilities.
Still, the report noted an increase in recruiting for independent medical practice ownership, which dwindled in recent years, with the majority of doctors today employed likely due to financial obstacles of starting a practice.
The increase in recruiting indicates possible renewed interest in these practice settings, particularly concierge medicine, which allows doctors to avoid the challenges of third-party payments, the report stated.
Grant said that despite the flexibility and financial autonomy of starting their own practice, new providers who choose this path face obstacles, such as competing with urgent care centers and retail health clinics, which have been on the rise in the past year.
Saddled with debt from medical training, most graduating residents will choose to work toward financial stability and then consider their own practice later in their career, she said.
Flexible Schedules
Work schedule/call hours or work-life balance was the biggest factor (36%) guiding residents’ choice of first post-residency positions compared with starting salary (19%), according to the Medscape Resident Salary & Debt Report 2024.
Grant said that larger practices and those closer to rural communities tend to offer more innovative work schedules, especially for certain specialists. Some solo practices that form partnerships could potentially allow flexible schedules such as 4-day work weeks or week-on-week-off arrangements, she added.
Physicians are also opting for the flexibility of temporary, locum tenens work to improve job conditions and address feelings of burnout. Dr. Kaydo, DO, as she’s known on Instagram, posts about her experiences as locum tenens. “I found that I could have more flexibility as a locum. I want to be able to take time off when I want and as long as I wanted,” said the full-time family medicine doctor who practices at an outpatient clinic in Philadelphia.
“Basically, I’m contract-working, and they pay me as much as I work, and I can also take more time off.” Her employer for the past year also allowed her to work 10 hours a day, 4 days a week instead of the more traditional 8-hour, 5-day schedule.
Dr. Kaydo said she believes many young doctors think contract employees don’t have a permanent job, are not guaranteed a certain salary, and could easily lose their jobs. “I’ve found that most places really need doctors and are willing to negotiate.”
She said primary care locum doctors are particularly in demand in rural clinics and urban underserved areas.
Nagy said he is considering being a nocturnist, an emergency medicine doctor who works nights, to have more control over his schedule, higher pay, and more flexible shifts. “I switch days and nights and that can be tiring.”
Bransden said job flexibility was her primary job criterion. “I have a young child, so I wanted to work part-time with the potential for even more flexibility down the line. I am working 3 days a week, 8-hour days with a 1-hour break. A 3-day work week came with a pay cut, but for me, it works and is what I need right now.”
A version of this article appeared on Medscape.com.
Roshan Bransden didn’t count how many job offers she received during her recently completed training in family medicine. “It was pretty nonstop throughout all of my PGY-3 year,” she said.
Most of the job opportunities were different from the type of position she sought or where she wanted to work. Bransden graduated from residency at Montefiore Hospital in New York and accepted a position as a primary care doctor in Miami, close to where she grew up and where her family lives.
More than half (56%) of all residents in AMN Healthcare’s 2023 Survey of Final-Year Medical Residents received 100 or more job solicitations during their training, the highest figure since the survey began more than 30 years ago, the staffing agency reported.
Employers are recruiting residents earlier, offering residency stipends of $1500 to $2500 up to 18 months before they finish their training if they commit to an employment contract, said Leah Grant, president of AMN Healthcare’s Physician Permanent Solutions division, specializing in doctor recruitment. She said that the company’s clients are already eyeing residents completing their training in 2026.
“The key for residents is not about finding a position but choosing the right one out of many.” Grant added that residents typically aren’t taught negotiation skills or how to evaluate job offers. They tend to choose a position based on location, but they should also consider work–life balance issues such as call schedules and whether incentives such as signing bonuses, relocation allowances, and student loan reimbursement offset the job’s time commitment.
“If you are a physician and you are willing to go anywhere, you will have hundreds of opportunities,” said Tibor Nagy, DO, an emergency medicine fellow who recently searched for jobs. “It depends on what they want out of their careers.”
Location Is a Key Consideration
Nagy said he had fewer options because he was limited by location, staying close to where his wife is finishing her internal medicine residency. He is completing his fellowship at Atrium Health Carolinas Medical Center in Charlotte, North Carolina, and preparing to return to Prisma Health in Greenville, South Carolina, where he did his residency.
He said that the job search was easier than he anticipated considering the tight market following a job report from the American College of Emergency Physicians in 2021 that predicted an oversupply of 8000 emergency medicine physicians by 2030.
Halfway through Nagy’s residency, he sought a fellowship in emergency medical services (EMS) to be more competitive in the job market. After that, “Every door I knocked on was open to hiring. Maybe it’s a regional thing. They were happy to interview me.”
In addition to location, Nagy’s top priorities when choosing a job were stability and being able to use his EMS fellowship to become a medical director of an EMS system, agency, or fire department. He wanted to work for a hospital system with an academic focus without much employee turnover.
Salary vs Benefits
AMN Healthcare received the most physician searches for family medicine doctors, followed by OB/GYNs. The staffing agency reported that close to two thirds (63%) of its search engagements during the 2023-2024 review period were for specialists, reflecting the needs of an aging population.
The highest average starting salaries were for surgical and internal medicine subspecialties, according to AMN Healthcare’s 2024 Physician and Advanced Practitioner Recruiting Incentives. Orthopedic surgery averaged $633,000; urology, $540,000; gastroenterology, $506,000; and pulmonary medicine, $418,000. For comparison, the average starting salaries for primary care doctors were family medicine, $255,000; internal medicine, $255,000; and pediatrics, $233,000.
In addition to starting salaries, many physicians receive signing bonuses, relocation allowances, and continuing medical education (CME) allowances. According to the report, the average signing bonus for physicians was $31,473. The average relocation allowance for physicians was $11,284 and the average CME allowance was $3969.
Salary wasn’t Nagy’s top priority when choosing a job, though he admits that the ability to pay back thousands of dollars in medical school loans will be helpful. Instead of focusing on higher pay to offset student loans, Nagy said he sought nonprofit positions to help him qualify for public service loan forgiveness.
The federal program forgives loan balances after the recipient makes monthly payments for 10 years while working for a government or nonprofit organization. He also racked up 3 years of residency and his fellowship year at nonprofit hospitals toward that commitment.
He said jobs that pay more may require doctors to see more patients. “The hustle may be different. There are definitely tradeoffs,” he said.
Bransden said the position she begins in January will allow her to work part-time with full benefits, among other perks. “My employer is a membership-based practice, so I’ll be able to gift a few memberships to family and friends.”
Going Solo
Mohammad Ibrahim, DO, is among a minority of new physicians who have chosen to set up their own practice.
Only 6% of residents in AMN Healthcare’s 2024 report indicated that a solo practice was among their top two choices, while 20% listed partnering with another physician.
Ibrahim is a sports medicine fellow at the University of Michigan Health-West in Wyoming, after finishing his family medicine residency at Trinity Health Livingston Hospital in Howell, Michigan.
After his fellowship ends, he said he plans to stay in Michigan, where his family lives.
Ibrahim said he began his medical education knowing he wanted to become a solo clinician in private practice. He sees it as a way to have more control over his decisions about patient care and business practices.
Working in a hospital often requires doctors to gain approval from several levels of authority for decisions such as ordering new equipment or forgiving part of a service payment. He also wanted to set his schedule to take Friday afternoons off for Muslim prayer.
Although he realizes the challenges of starting a private practice, Ibrahim said those who go through graduate medical education can figure out how to adapt and overcome any obstacles. “I think it’s more doable than we are led to believe.”
He said that if more residents were exposed to private practice, they might pursue that path. During his training, Ibrahim did a rotation with a private practice physician. “It’s nice to see people proud of what they built, what they contributed.”
Most residents don’t choose private practice. In the AMN Healthcare survey, 68% of residents said that employment by a hospital was among their top two choices for a practice setting, 42% said employment by a single-specialty group, and 32%, employment by a multispecialty group.
Of the majority of job searches AMN Healthcare conducted, 28% were to fill positions in hospital settings, followed by 26% for medical groups, 22% for academic medical centers, 13% for urgent care centers and retail clinics, 6% for solo practices, partnerships, or concierge practice settings, and 5% for Federally Qualified Health Centers/Community Health Centers or Indian Health facilities.
Still, the report noted an increase in recruiting for independent medical practice ownership, which dwindled in recent years, with the majority of doctors today employed likely due to financial obstacles of starting a practice.
The increase in recruiting indicates possible renewed interest in these practice settings, particularly concierge medicine, which allows doctors to avoid the challenges of third-party payments, the report stated.
Grant said that despite the flexibility and financial autonomy of starting their own practice, new providers who choose this path face obstacles, such as competing with urgent care centers and retail health clinics, which have been on the rise in the past year.
Saddled with debt from medical training, most graduating residents will choose to work toward financial stability and then consider their own practice later in their career, she said.
Flexible Schedules
Work schedule/call hours or work-life balance was the biggest factor (36%) guiding residents’ choice of first post-residency positions compared with starting salary (19%), according to the Medscape Resident Salary & Debt Report 2024.
Grant said that larger practices and those closer to rural communities tend to offer more innovative work schedules, especially for certain specialists. Some solo practices that form partnerships could potentially allow flexible schedules such as 4-day work weeks or week-on-week-off arrangements, she added.
Physicians are also opting for the flexibility of temporary, locum tenens work to improve job conditions and address feelings of burnout. Dr. Kaydo, DO, as she’s known on Instagram, posts about her experiences as locum tenens. “I found that I could have more flexibility as a locum. I want to be able to take time off when I want and as long as I wanted,” said the full-time family medicine doctor who practices at an outpatient clinic in Philadelphia.
“Basically, I’m contract-working, and they pay me as much as I work, and I can also take more time off.” Her employer for the past year also allowed her to work 10 hours a day, 4 days a week instead of the more traditional 8-hour, 5-day schedule.
Dr. Kaydo said she believes many young doctors think contract employees don’t have a permanent job, are not guaranteed a certain salary, and could easily lose their jobs. “I’ve found that most places really need doctors and are willing to negotiate.”
She said primary care locum doctors are particularly in demand in rural clinics and urban underserved areas.
Nagy said he is considering being a nocturnist, an emergency medicine doctor who works nights, to have more control over his schedule, higher pay, and more flexible shifts. “I switch days and nights and that can be tiring.”
Bransden said job flexibility was her primary job criterion. “I have a young child, so I wanted to work part-time with the potential for even more flexibility down the line. I am working 3 days a week, 8-hour days with a 1-hour break. A 3-day work week came with a pay cut, but for me, it works and is what I need right now.”
A version of this article appeared on Medscape.com.
New Cancer Drugs: Do Patients Prefer Faster Access or Clinical Benefit?
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY
Alcohol: How Much Is Too Much?
A 40-year-old woman presents for a wellness visit. She says that she feels well but admits to high levels of stress and occasional fatigue. She works about 60 hours per week as an executive in a finance company. In addition, she is married and has two children, ages 12 and 10 years. She says that she has no time for herself and has noticed that she gets frustrated faster than she used to, but she does not think she has depression. Her score on a Patient Health Questionnaire 9 (PHQ-9) is 5, indicating a low level of depression symptoms.
Regarding health habits, she has never used nicotine products. She reports having one to two alcoholic drinks per day, either wine or a cocktail, and has four drinks per day on a couple of weekend days per month (such as on “date night” with her spouse). She says she does not use any other drugs, including cannabis, and is not taking any medications.
Her vital signs and physical examination are unremarkable. You note that she had an evaluation with a complete blood count, comprehensive metabolic panel, and thyroid-stimulating hormone level performed 7 months ago, with normal results.
What would be the best next step in caring for this patient?
A. Ask her to consider talk therapy to address her fatigue and stress
B. Have her complete a tool (such as the AUDIT-C) to identify hazardous drinking
C. Consider prescribing a selective serotonin reuptake inhibitor
D. Repeat her previous labs, adding vitamin B12 and vitamin D levels
Dr. Vega’s Take
Although all of the answer choices above could apply to this patient, a more formal screening for problem drinking is the most important intervention to make now.
This patient’s story is not unique, particularly in the wake of the COVID-19 pandemic. According to data from the National Institute on Alcohol Abuse and Alcoholism, 64% and 61% of males and females, respectively, at least 12 years of age, reported consuming alcohol in 2023, and 21.7% of these individuals reported binge drinking.
Alcohol consumption is taking an increasing toll on public health. Between 2016 and 2021, the number of US deaths caused by excessive alcohol use increased by 29%, to a total of 47.6 cases per 100,000 population. The death rate increased faster among females vs males.
The US Preventive Services Task Force (USPSTF) recommends screening for alcohol misuse among adults at least 18 years of age, with no specific interval for repeat screening. USPSTF does recommend two specific screening instruments because of their ease of use and accuracy: the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) and Single Alcohol Screening Question (SASQ): How many times in the past year have you had more than four drinks (for women) or five drinks (for men) in a day?
The AUDIT-C features three questions about alcohol use, the amount of alcohol consumed, and the frequency of heavy alcohol use. The instrument is scored from 0 to 12, with a higher score indicating a high risk for problem drinking. Generally, an AUDIT-C score is considered a positive screen at a score of 4 for men and 3 for women. The SASQ focuses on the number of heavy drinking days in the past year, with a current cutoff of five drinks for men and four drinks for women and anyone age 65 years or older.
Both the AUDIT-C and SASQ should be followed up with a more extensive history to make the diagnosis of alcohol use disorder (AUD). The USPSTF also recommends at least brief follow-up counseling for adults with possible AUD, noting that the most common form of counseling is personalized normative feedback, which compares a patient’s alcohol use pattern with that of others.
What is your practice in screening for AUD, and what have you found effective in counseling patients? I look forward to hearing your thoughts.
Dr. Vega is Health Sciences Clinical Professor, Family Medicine, University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.
A version of this article first appeared on Medscape.com.
A 40-year-old woman presents for a wellness visit. She says that she feels well but admits to high levels of stress and occasional fatigue. She works about 60 hours per week as an executive in a finance company. In addition, she is married and has two children, ages 12 and 10 years. She says that she has no time for herself and has noticed that she gets frustrated faster than she used to, but she does not think she has depression. Her score on a Patient Health Questionnaire 9 (PHQ-9) is 5, indicating a low level of depression symptoms.
Regarding health habits, she has never used nicotine products. She reports having one to two alcoholic drinks per day, either wine or a cocktail, and has four drinks per day on a couple of weekend days per month (such as on “date night” with her spouse). She says she does not use any other drugs, including cannabis, and is not taking any medications.
Her vital signs and physical examination are unremarkable. You note that she had an evaluation with a complete blood count, comprehensive metabolic panel, and thyroid-stimulating hormone level performed 7 months ago, with normal results.
What would be the best next step in caring for this patient?
A. Ask her to consider talk therapy to address her fatigue and stress
B. Have her complete a tool (such as the AUDIT-C) to identify hazardous drinking
C. Consider prescribing a selective serotonin reuptake inhibitor
D. Repeat her previous labs, adding vitamin B12 and vitamin D levels
Dr. Vega’s Take
Although all of the answer choices above could apply to this patient, a more formal screening for problem drinking is the most important intervention to make now.
This patient’s story is not unique, particularly in the wake of the COVID-19 pandemic. According to data from the National Institute on Alcohol Abuse and Alcoholism, 64% and 61% of males and females, respectively, at least 12 years of age, reported consuming alcohol in 2023, and 21.7% of these individuals reported binge drinking.
Alcohol consumption is taking an increasing toll on public health. Between 2016 and 2021, the number of US deaths caused by excessive alcohol use increased by 29%, to a total of 47.6 cases per 100,000 population. The death rate increased faster among females vs males.
The US Preventive Services Task Force (USPSTF) recommends screening for alcohol misuse among adults at least 18 years of age, with no specific interval for repeat screening. USPSTF does recommend two specific screening instruments because of their ease of use and accuracy: the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) and Single Alcohol Screening Question (SASQ): How many times in the past year have you had more than four drinks (for women) or five drinks (for men) in a day?
The AUDIT-C features three questions about alcohol use, the amount of alcohol consumed, and the frequency of heavy alcohol use. The instrument is scored from 0 to 12, with a higher score indicating a high risk for problem drinking. Generally, an AUDIT-C score is considered a positive screen at a score of 4 for men and 3 for women. The SASQ focuses on the number of heavy drinking days in the past year, with a current cutoff of five drinks for men and four drinks for women and anyone age 65 years or older.
Both the AUDIT-C and SASQ should be followed up with a more extensive history to make the diagnosis of alcohol use disorder (AUD). The USPSTF also recommends at least brief follow-up counseling for adults with possible AUD, noting that the most common form of counseling is personalized normative feedback, which compares a patient’s alcohol use pattern with that of others.
What is your practice in screening for AUD, and what have you found effective in counseling patients? I look forward to hearing your thoughts.
Dr. Vega is Health Sciences Clinical Professor, Family Medicine, University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.
A version of this article first appeared on Medscape.com.
A 40-year-old woman presents for a wellness visit. She says that she feels well but admits to high levels of stress and occasional fatigue. She works about 60 hours per week as an executive in a finance company. In addition, she is married and has two children, ages 12 and 10 years. She says that she has no time for herself and has noticed that she gets frustrated faster than she used to, but she does not think she has depression. Her score on a Patient Health Questionnaire 9 (PHQ-9) is 5, indicating a low level of depression symptoms.
Regarding health habits, she has never used nicotine products. She reports having one to two alcoholic drinks per day, either wine or a cocktail, and has four drinks per day on a couple of weekend days per month (such as on “date night” with her spouse). She says she does not use any other drugs, including cannabis, and is not taking any medications.
Her vital signs and physical examination are unremarkable. You note that she had an evaluation with a complete blood count, comprehensive metabolic panel, and thyroid-stimulating hormone level performed 7 months ago, with normal results.
What would be the best next step in caring for this patient?
A. Ask her to consider talk therapy to address her fatigue and stress
B. Have her complete a tool (such as the AUDIT-C) to identify hazardous drinking
C. Consider prescribing a selective serotonin reuptake inhibitor
D. Repeat her previous labs, adding vitamin B12 and vitamin D levels
Dr. Vega’s Take
Although all of the answer choices above could apply to this patient, a more formal screening for problem drinking is the most important intervention to make now.
This patient’s story is not unique, particularly in the wake of the COVID-19 pandemic. According to data from the National Institute on Alcohol Abuse and Alcoholism, 64% and 61% of males and females, respectively, at least 12 years of age, reported consuming alcohol in 2023, and 21.7% of these individuals reported binge drinking.
Alcohol consumption is taking an increasing toll on public health. Between 2016 and 2021, the number of US deaths caused by excessive alcohol use increased by 29%, to a total of 47.6 cases per 100,000 population. The death rate increased faster among females vs males.
The US Preventive Services Task Force (USPSTF) recommends screening for alcohol misuse among adults at least 18 years of age, with no specific interval for repeat screening. USPSTF does recommend two specific screening instruments because of their ease of use and accuracy: the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) and Single Alcohol Screening Question (SASQ): How many times in the past year have you had more than four drinks (for women) or five drinks (for men) in a day?
The AUDIT-C features three questions about alcohol use, the amount of alcohol consumed, and the frequency of heavy alcohol use. The instrument is scored from 0 to 12, with a higher score indicating a high risk for problem drinking. Generally, an AUDIT-C score is considered a positive screen at a score of 4 for men and 3 for women. The SASQ focuses on the number of heavy drinking days in the past year, with a current cutoff of five drinks for men and four drinks for women and anyone age 65 years or older.
Both the AUDIT-C and SASQ should be followed up with a more extensive history to make the diagnosis of alcohol use disorder (AUD). The USPSTF also recommends at least brief follow-up counseling for adults with possible AUD, noting that the most common form of counseling is personalized normative feedback, which compares a patient’s alcohol use pattern with that of others.
What is your practice in screening for AUD, and what have you found effective in counseling patients? I look forward to hearing your thoughts.
Dr. Vega is Health Sciences Clinical Professor, Family Medicine, University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Geriatric Dermatology: Q&A With Daniel C. Butler, MD
Daniel C. Butler, MD, is associate professor of dermatology and director of the new Inflammatory and Aging Skin Research Program in the Division of Dermatology at the University of Arizona College of Medicine, Tucson, Arizona. Before returning to Arizona, where he had attended medical school, Butler practiced and was a researcher at the University of California, San Francisco, and its geriatric dermatology clinic. He is a co-founder and continues to co-lead the American Academy of Dermatology (AAD) Geriatric Dermatology Expert Resource Group (ERG).
Butler’s interest in geriatric dermatology is rooted in his experience growing up with four grandparents and witnessing their wisdom, relationships, moments with loved ones, and other unique and desirable parts of growing old. “When I looked later at how aging was perceived in dermatology, I found it was a lot about ‘antiaging,’” he told this news organization. “I thought there was a needed voice in dermatology for healthy aging, for all the desirable things that only growing old can provide, along with all the incredible ‘antiaging’ things we can do.”
In interviews, Butler spoke about research priorities in geriatric dermatology, how the “4M” model of geriatrics should be applied within dermatology, how dermatologists can best work with older complex patients, and more. The conversation was edited for clarity and length.
What is geriatric dermatology? It is described by the AAD’s Geriatric Dermatology ERG as “an emerging subspecialty.” Yet it’s also viewed more broadly. Please speak about its various identities and meanings and its importance for dermatology.
If you’re a Mohs surgeon, you’re seeing a strong majority of over 65 patients. And in various specialty clinics, such as inflammatory skin disease, geriatric dermatology pertains to you. In many ways, it can be viewed as a mindset.
From a framework standpoint, and as a field, geriatric dermatology is a basic science initiative, a clinical initiative, an educational initiative, and an advocacy initiative. The goal is to be able to influence, grow, and learn in each of these categories for our older patients. This is happening: Research in this field has progressed, and education has progressed, which has driven some progress in clinical care.
How has research progressed in the basic science of aging skin? What are key questions for dermatology?
There has been a lot of basic science research on aging skin and on how an aging immune system, for instance, is reflected in conditions such as bullous pemphigoid, atopic dermatitis (AD), and chronic itch. But aging involves more than immunosenescence. I think of aging skin as a three-headed monster that involves changes in the skin barrier and the microbiome as well. But is there a primary piece of aging in the skin? What comes first or influences the other? More research on these questions can potentially influence our treatments.
With respect to the immune system, what we’re finding in the skin is that age-related change is not a decline in the immune system per se, but rather aberrance in response. Parts of the system tend to become overactive, with a skew toward overexpression of type 2 inflammation. This can be problematic, driving conditions such as chronic itch.
With respect to the skin barrier, we lose essential fatty acids, and we lose a lot of our recovery ability and our ability to respond quickly to environmental stressors. But are barrier changes triggering the immune system? Or is it the other way around?
The microbiome, which is a big focus of research, involves similar chicken-and-egg discussions. Is it the microbiome that changes and alters the barrier, which then entices the immune system? Which one happens first? We have a lot to learn, and there’s probably not one answer for every patient.
Please speak about research more broadly. What questions and issues need to be answered and addressed to improve the dermatologic care of older adults?
In general, research in dermatology is very disease-specific and not particularly conducive to looking at the larger demographic populations. We have a huge opportunity, therefore, to break the mold and grow geriatric dermatology as an area of population-based research — so that geriatric dermatology research encompasses not only the melanoma researcher who’s trying to understand how aging influences the melanocytes but also the epidemiologic researcher looking at how our diagnoses and coding and prescription practices are different in the 65-plus age group.
Clinically speaking, researchers want to better understand how aging influences the clinical presentations of our diseases. And there’s research to be done on best practices. For example, what are the best practices for treating basal cell carcinomas in patients with mild cognitive impairment? How should we consider the use of topicals in a patient who has severe arthritis or who lives alone? And then how should we teach practical approaches to help providers meet people where they are?
Looking at it from a healthcare system standpoint, there are many care delivery and access issues — practical pieces — to research, and we’re getting a lot better with this. We’re also advocating not only for more inclusion of older adults in clinical trials of treatments but also for the use of evaluations and outcomes that are relevant and important for older adults.
One piece of good news is that we’re seeing safer treatment options with tremendous efficacy that target known pathways for diseases like AD and chronic itch that affect older adults. Again, now we must find ways to improve access to these novel, safe options.
Our research program at the University of Arizona College of Medicine, which we’re just getting off the ground, aims to be dual-sided, looking both at the basic science of aging skin and at access and care delivery issues, such as how to ensure that patients on Medicare have access to medications that are at least on par with others with private insurance.
What are the most common dermatologic problems experienced by older adults?
Based on my experience and on research that we expect to be published soon, it’s absolutely nonmelanoma skin cancers, precancers like actinic keratoses — and on the inflammatory disease side, itch, AD, and psoriasis. Of course, also common are the age-related changes to the skin that we put in the benign category, such as solar lentigines.
How does age influence dermatologic diseases from a pathophysiological and clinical standpoint?
Diseases overall are very similar and respond to the same treatments, but age in and of itself does influence little pieces. For example, there is more crossover in the presentation of psoriasis and AD in older adults, leading to delays in the diagnosis of psoriasis.
With AD, we’ve found that itch is the predominant symptom for older adults rather than the red rash. We see higher or more severe itch scores in older adults with AD with less visual changes on the skin than in younger cohorts. And rash occurs in different locations than in young patients. Older adults typically present with it on their chest, back, and across the trunk, rather than in folded areas. They’re also more likely to get it on their legs in a nummular pattern as opposed to the more traditional flexural area presentation.
What unique considerations need to be made in treating older adults? How should the 4M model of geriatrics be applied to dermatologic care?
Our care model pushes us to be very algorithmic, but at the end of the day, what’s really important are the 4Ms: Mobility, medication, mentation, and “what matters most.” As you’re having your shared decision-making conversations with your patients and their families, these should be your priorities.
A patient with physical limitations, for instance, may not be able to apply a topical cream twice a day all over the body. They may have comorbidities and treatments for these comorbidities that may conflict with medications you’re considering.
And then mentation is so important. For a long time, we used antihistamines for older adults, but this has been proven to be bad for their mentation and risky in other ways. We need to be sure we’re prioritizing their ability to be clear mentally when we’re prescribing medications and even when we’re considering surgical approaches. Do they show capacity for that procedure or treatment, and how will they respond to that treatment later on?
Using the 4M model to drive conversations is a way to get all of us to connect to the patient and learn about what’s most important for them. In many ways, geriatrics is about taking a step back from your specialist skills and thinking about how you would want a family member treated.
We want to avoid treating just the lesion or the pathologic diagnosis. We want to avoid the “conveyor belt” from a biopsy to Mohs. I have 95-year-olds who say, “Heck yeah, if Mohs is the best treatment, that’s what I want.” And I have 70-year-olds who say, “I think I’ll go with another option,” and that’s the right decision for them. It’s having the conversation that matters.
In practice, given time constraints and other confines, how can dermatologists best work with more complex older patients? What are your practical tips?
People talk about having 45-minute “golden year” conversations with their older patients, but it doesn’t have to be this way. In pursuing geriatric dermatology, I decided early on that I wanted to make sure it was practical, so I’ve focused on maximizing shorter visits and on embracing the concept that relationships can be developed over time. Each time we meet with someone, we’re building equity to have bigger conversations later on.
I can have a 15-minute conversation about whether my patient may want to have Mohs surgery, for instance, or escalate treatment to a systemic agent for their chronic inflammatory disease. If that time isn’t enough, I can encourage further thought about treatment options, acknowledge that decisions aren’t necessarily easy, and schedule a follow-up or offer to call the patient after clinic to continue the conversation.
Sometimes, when I’m at an impasse and my patient is unsure how to proceed, I’ll use clear metrics relevant to older adults — sleep, activity level, and caregiver burden — to help my patient. If someone is not sleeping because of their lesion — if they’re so itchy or their inflammatory disease is uncontrolled, for instance — I’ll point out that the side effects of not sleeping are worse than the medications or surgery we’d pursue. If someone removes themselves from an activity due to their skin condition, that’s a red flag. And if the caregiver in the room is overwhelmed or frustrated by having to put cream on twice a day, I’ll use this to advance treatment.
What resources are available for dermatologists interested in improving their geriatric dermatology skills or advancing the area?
For those interested in investigating these issues or improving their practices, the AAD’s Geriatric Dermatology ERG is always welcoming of new members. The ERG will have an all-inclusive meeting at the 2025 annual AAD meeting in March.
The AAD also has educational modules on geriatric dermatology that were recently published as an initiative of our ERG. More information is available on the website. Also valuable is the ElderDerm conference hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC; the second such conference takes place in May 2025.
Butler reported that he had no relevant financial disclosures.
A version of this article appeared on Medscape.com.
Daniel C. Butler, MD, is associate professor of dermatology and director of the new Inflammatory and Aging Skin Research Program in the Division of Dermatology at the University of Arizona College of Medicine, Tucson, Arizona. Before returning to Arizona, where he had attended medical school, Butler practiced and was a researcher at the University of California, San Francisco, and its geriatric dermatology clinic. He is a co-founder and continues to co-lead the American Academy of Dermatology (AAD) Geriatric Dermatology Expert Resource Group (ERG).
Butler’s interest in geriatric dermatology is rooted in his experience growing up with four grandparents and witnessing their wisdom, relationships, moments with loved ones, and other unique and desirable parts of growing old. “When I looked later at how aging was perceived in dermatology, I found it was a lot about ‘antiaging,’” he told this news organization. “I thought there was a needed voice in dermatology for healthy aging, for all the desirable things that only growing old can provide, along with all the incredible ‘antiaging’ things we can do.”
In interviews, Butler spoke about research priorities in geriatric dermatology, how the “4M” model of geriatrics should be applied within dermatology, how dermatologists can best work with older complex patients, and more. The conversation was edited for clarity and length.
What is geriatric dermatology? It is described by the AAD’s Geriatric Dermatology ERG as “an emerging subspecialty.” Yet it’s also viewed more broadly. Please speak about its various identities and meanings and its importance for dermatology.
If you’re a Mohs surgeon, you’re seeing a strong majority of over 65 patients. And in various specialty clinics, such as inflammatory skin disease, geriatric dermatology pertains to you. In many ways, it can be viewed as a mindset.
From a framework standpoint, and as a field, geriatric dermatology is a basic science initiative, a clinical initiative, an educational initiative, and an advocacy initiative. The goal is to be able to influence, grow, and learn in each of these categories for our older patients. This is happening: Research in this field has progressed, and education has progressed, which has driven some progress in clinical care.
How has research progressed in the basic science of aging skin? What are key questions for dermatology?
There has been a lot of basic science research on aging skin and on how an aging immune system, for instance, is reflected in conditions such as bullous pemphigoid, atopic dermatitis (AD), and chronic itch. But aging involves more than immunosenescence. I think of aging skin as a three-headed monster that involves changes in the skin barrier and the microbiome as well. But is there a primary piece of aging in the skin? What comes first or influences the other? More research on these questions can potentially influence our treatments.
With respect to the immune system, what we’re finding in the skin is that age-related change is not a decline in the immune system per se, but rather aberrance in response. Parts of the system tend to become overactive, with a skew toward overexpression of type 2 inflammation. This can be problematic, driving conditions such as chronic itch.
With respect to the skin barrier, we lose essential fatty acids, and we lose a lot of our recovery ability and our ability to respond quickly to environmental stressors. But are barrier changes triggering the immune system? Or is it the other way around?
The microbiome, which is a big focus of research, involves similar chicken-and-egg discussions. Is it the microbiome that changes and alters the barrier, which then entices the immune system? Which one happens first? We have a lot to learn, and there’s probably not one answer for every patient.
Please speak about research more broadly. What questions and issues need to be answered and addressed to improve the dermatologic care of older adults?
In general, research in dermatology is very disease-specific and not particularly conducive to looking at the larger demographic populations. We have a huge opportunity, therefore, to break the mold and grow geriatric dermatology as an area of population-based research — so that geriatric dermatology research encompasses not only the melanoma researcher who’s trying to understand how aging influences the melanocytes but also the epidemiologic researcher looking at how our diagnoses and coding and prescription practices are different in the 65-plus age group.
Clinically speaking, researchers want to better understand how aging influences the clinical presentations of our diseases. And there’s research to be done on best practices. For example, what are the best practices for treating basal cell carcinomas in patients with mild cognitive impairment? How should we consider the use of topicals in a patient who has severe arthritis or who lives alone? And then how should we teach practical approaches to help providers meet people where they are?
Looking at it from a healthcare system standpoint, there are many care delivery and access issues — practical pieces — to research, and we’re getting a lot better with this. We’re also advocating not only for more inclusion of older adults in clinical trials of treatments but also for the use of evaluations and outcomes that are relevant and important for older adults.
One piece of good news is that we’re seeing safer treatment options with tremendous efficacy that target known pathways for diseases like AD and chronic itch that affect older adults. Again, now we must find ways to improve access to these novel, safe options.
Our research program at the University of Arizona College of Medicine, which we’re just getting off the ground, aims to be dual-sided, looking both at the basic science of aging skin and at access and care delivery issues, such as how to ensure that patients on Medicare have access to medications that are at least on par with others with private insurance.
What are the most common dermatologic problems experienced by older adults?
Based on my experience and on research that we expect to be published soon, it’s absolutely nonmelanoma skin cancers, precancers like actinic keratoses — and on the inflammatory disease side, itch, AD, and psoriasis. Of course, also common are the age-related changes to the skin that we put in the benign category, such as solar lentigines.
How does age influence dermatologic diseases from a pathophysiological and clinical standpoint?
Diseases overall are very similar and respond to the same treatments, but age in and of itself does influence little pieces. For example, there is more crossover in the presentation of psoriasis and AD in older adults, leading to delays in the diagnosis of psoriasis.
With AD, we’ve found that itch is the predominant symptom for older adults rather than the red rash. We see higher or more severe itch scores in older adults with AD with less visual changes on the skin than in younger cohorts. And rash occurs in different locations than in young patients. Older adults typically present with it on their chest, back, and across the trunk, rather than in folded areas. They’re also more likely to get it on their legs in a nummular pattern as opposed to the more traditional flexural area presentation.
What unique considerations need to be made in treating older adults? How should the 4M model of geriatrics be applied to dermatologic care?
Our care model pushes us to be very algorithmic, but at the end of the day, what’s really important are the 4Ms: Mobility, medication, mentation, and “what matters most.” As you’re having your shared decision-making conversations with your patients and their families, these should be your priorities.
A patient with physical limitations, for instance, may not be able to apply a topical cream twice a day all over the body. They may have comorbidities and treatments for these comorbidities that may conflict with medications you’re considering.
And then mentation is so important. For a long time, we used antihistamines for older adults, but this has been proven to be bad for their mentation and risky in other ways. We need to be sure we’re prioritizing their ability to be clear mentally when we’re prescribing medications and even when we’re considering surgical approaches. Do they show capacity for that procedure or treatment, and how will they respond to that treatment later on?
Using the 4M model to drive conversations is a way to get all of us to connect to the patient and learn about what’s most important for them. In many ways, geriatrics is about taking a step back from your specialist skills and thinking about how you would want a family member treated.
We want to avoid treating just the lesion or the pathologic diagnosis. We want to avoid the “conveyor belt” from a biopsy to Mohs. I have 95-year-olds who say, “Heck yeah, if Mohs is the best treatment, that’s what I want.” And I have 70-year-olds who say, “I think I’ll go with another option,” and that’s the right decision for them. It’s having the conversation that matters.
In practice, given time constraints and other confines, how can dermatologists best work with more complex older patients? What are your practical tips?
People talk about having 45-minute “golden year” conversations with their older patients, but it doesn’t have to be this way. In pursuing geriatric dermatology, I decided early on that I wanted to make sure it was practical, so I’ve focused on maximizing shorter visits and on embracing the concept that relationships can be developed over time. Each time we meet with someone, we’re building equity to have bigger conversations later on.
I can have a 15-minute conversation about whether my patient may want to have Mohs surgery, for instance, or escalate treatment to a systemic agent for their chronic inflammatory disease. If that time isn’t enough, I can encourage further thought about treatment options, acknowledge that decisions aren’t necessarily easy, and schedule a follow-up or offer to call the patient after clinic to continue the conversation.
Sometimes, when I’m at an impasse and my patient is unsure how to proceed, I’ll use clear metrics relevant to older adults — sleep, activity level, and caregiver burden — to help my patient. If someone is not sleeping because of their lesion — if they’re so itchy or their inflammatory disease is uncontrolled, for instance — I’ll point out that the side effects of not sleeping are worse than the medications or surgery we’d pursue. If someone removes themselves from an activity due to their skin condition, that’s a red flag. And if the caregiver in the room is overwhelmed or frustrated by having to put cream on twice a day, I’ll use this to advance treatment.
What resources are available for dermatologists interested in improving their geriatric dermatology skills or advancing the area?
For those interested in investigating these issues or improving their practices, the AAD’s Geriatric Dermatology ERG is always welcoming of new members. The ERG will have an all-inclusive meeting at the 2025 annual AAD meeting in March.
The AAD also has educational modules on geriatric dermatology that were recently published as an initiative of our ERG. More information is available on the website. Also valuable is the ElderDerm conference hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC; the second such conference takes place in May 2025.
Butler reported that he had no relevant financial disclosures.
A version of this article appeared on Medscape.com.
Daniel C. Butler, MD, is associate professor of dermatology and director of the new Inflammatory and Aging Skin Research Program in the Division of Dermatology at the University of Arizona College of Medicine, Tucson, Arizona. Before returning to Arizona, where he had attended medical school, Butler practiced and was a researcher at the University of California, San Francisco, and its geriatric dermatology clinic. He is a co-founder and continues to co-lead the American Academy of Dermatology (AAD) Geriatric Dermatology Expert Resource Group (ERG).
Butler’s interest in geriatric dermatology is rooted in his experience growing up with four grandparents and witnessing their wisdom, relationships, moments with loved ones, and other unique and desirable parts of growing old. “When I looked later at how aging was perceived in dermatology, I found it was a lot about ‘antiaging,’” he told this news organization. “I thought there was a needed voice in dermatology for healthy aging, for all the desirable things that only growing old can provide, along with all the incredible ‘antiaging’ things we can do.”
In interviews, Butler spoke about research priorities in geriatric dermatology, how the “4M” model of geriatrics should be applied within dermatology, how dermatologists can best work with older complex patients, and more. The conversation was edited for clarity and length.
What is geriatric dermatology? It is described by the AAD’s Geriatric Dermatology ERG as “an emerging subspecialty.” Yet it’s also viewed more broadly. Please speak about its various identities and meanings and its importance for dermatology.
If you’re a Mohs surgeon, you’re seeing a strong majority of over 65 patients. And in various specialty clinics, such as inflammatory skin disease, geriatric dermatology pertains to you. In many ways, it can be viewed as a mindset.
From a framework standpoint, and as a field, geriatric dermatology is a basic science initiative, a clinical initiative, an educational initiative, and an advocacy initiative. The goal is to be able to influence, grow, and learn in each of these categories for our older patients. This is happening: Research in this field has progressed, and education has progressed, which has driven some progress in clinical care.
How has research progressed in the basic science of aging skin? What are key questions for dermatology?
There has been a lot of basic science research on aging skin and on how an aging immune system, for instance, is reflected in conditions such as bullous pemphigoid, atopic dermatitis (AD), and chronic itch. But aging involves more than immunosenescence. I think of aging skin as a three-headed monster that involves changes in the skin barrier and the microbiome as well. But is there a primary piece of aging in the skin? What comes first or influences the other? More research on these questions can potentially influence our treatments.
With respect to the immune system, what we’re finding in the skin is that age-related change is not a decline in the immune system per se, but rather aberrance in response. Parts of the system tend to become overactive, with a skew toward overexpression of type 2 inflammation. This can be problematic, driving conditions such as chronic itch.
With respect to the skin barrier, we lose essential fatty acids, and we lose a lot of our recovery ability and our ability to respond quickly to environmental stressors. But are barrier changes triggering the immune system? Or is it the other way around?
The microbiome, which is a big focus of research, involves similar chicken-and-egg discussions. Is it the microbiome that changes and alters the barrier, which then entices the immune system? Which one happens first? We have a lot to learn, and there’s probably not one answer for every patient.
Please speak about research more broadly. What questions and issues need to be answered and addressed to improve the dermatologic care of older adults?
In general, research in dermatology is very disease-specific and not particularly conducive to looking at the larger demographic populations. We have a huge opportunity, therefore, to break the mold and grow geriatric dermatology as an area of population-based research — so that geriatric dermatology research encompasses not only the melanoma researcher who’s trying to understand how aging influences the melanocytes but also the epidemiologic researcher looking at how our diagnoses and coding and prescription practices are different in the 65-plus age group.
Clinically speaking, researchers want to better understand how aging influences the clinical presentations of our diseases. And there’s research to be done on best practices. For example, what are the best practices for treating basal cell carcinomas in patients with mild cognitive impairment? How should we consider the use of topicals in a patient who has severe arthritis or who lives alone? And then how should we teach practical approaches to help providers meet people where they are?
Looking at it from a healthcare system standpoint, there are many care delivery and access issues — practical pieces — to research, and we’re getting a lot better with this. We’re also advocating not only for more inclusion of older adults in clinical trials of treatments but also for the use of evaluations and outcomes that are relevant and important for older adults.
One piece of good news is that we’re seeing safer treatment options with tremendous efficacy that target known pathways for diseases like AD and chronic itch that affect older adults. Again, now we must find ways to improve access to these novel, safe options.
Our research program at the University of Arizona College of Medicine, which we’re just getting off the ground, aims to be dual-sided, looking both at the basic science of aging skin and at access and care delivery issues, such as how to ensure that patients on Medicare have access to medications that are at least on par with others with private insurance.
What are the most common dermatologic problems experienced by older adults?
Based on my experience and on research that we expect to be published soon, it’s absolutely nonmelanoma skin cancers, precancers like actinic keratoses — and on the inflammatory disease side, itch, AD, and psoriasis. Of course, also common are the age-related changes to the skin that we put in the benign category, such as solar lentigines.
How does age influence dermatologic diseases from a pathophysiological and clinical standpoint?
Diseases overall are very similar and respond to the same treatments, but age in and of itself does influence little pieces. For example, there is more crossover in the presentation of psoriasis and AD in older adults, leading to delays in the diagnosis of psoriasis.
With AD, we’ve found that itch is the predominant symptom for older adults rather than the red rash. We see higher or more severe itch scores in older adults with AD with less visual changes on the skin than in younger cohorts. And rash occurs in different locations than in young patients. Older adults typically present with it on their chest, back, and across the trunk, rather than in folded areas. They’re also more likely to get it on their legs in a nummular pattern as opposed to the more traditional flexural area presentation.
What unique considerations need to be made in treating older adults? How should the 4M model of geriatrics be applied to dermatologic care?
Our care model pushes us to be very algorithmic, but at the end of the day, what’s really important are the 4Ms: Mobility, medication, mentation, and “what matters most.” As you’re having your shared decision-making conversations with your patients and their families, these should be your priorities.
A patient with physical limitations, for instance, may not be able to apply a topical cream twice a day all over the body. They may have comorbidities and treatments for these comorbidities that may conflict with medications you’re considering.
And then mentation is so important. For a long time, we used antihistamines for older adults, but this has been proven to be bad for their mentation and risky in other ways. We need to be sure we’re prioritizing their ability to be clear mentally when we’re prescribing medications and even when we’re considering surgical approaches. Do they show capacity for that procedure or treatment, and how will they respond to that treatment later on?
Using the 4M model to drive conversations is a way to get all of us to connect to the patient and learn about what’s most important for them. In many ways, geriatrics is about taking a step back from your specialist skills and thinking about how you would want a family member treated.
We want to avoid treating just the lesion or the pathologic diagnosis. We want to avoid the “conveyor belt” from a biopsy to Mohs. I have 95-year-olds who say, “Heck yeah, if Mohs is the best treatment, that’s what I want.” And I have 70-year-olds who say, “I think I’ll go with another option,” and that’s the right decision for them. It’s having the conversation that matters.
In practice, given time constraints and other confines, how can dermatologists best work with more complex older patients? What are your practical tips?
People talk about having 45-minute “golden year” conversations with their older patients, but it doesn’t have to be this way. In pursuing geriatric dermatology, I decided early on that I wanted to make sure it was practical, so I’ve focused on maximizing shorter visits and on embracing the concept that relationships can be developed over time. Each time we meet with someone, we’re building equity to have bigger conversations later on.
I can have a 15-minute conversation about whether my patient may want to have Mohs surgery, for instance, or escalate treatment to a systemic agent for their chronic inflammatory disease. If that time isn’t enough, I can encourage further thought about treatment options, acknowledge that decisions aren’t necessarily easy, and schedule a follow-up or offer to call the patient after clinic to continue the conversation.
Sometimes, when I’m at an impasse and my patient is unsure how to proceed, I’ll use clear metrics relevant to older adults — sleep, activity level, and caregiver burden — to help my patient. If someone is not sleeping because of their lesion — if they’re so itchy or their inflammatory disease is uncontrolled, for instance — I’ll point out that the side effects of not sleeping are worse than the medications or surgery we’d pursue. If someone removes themselves from an activity due to their skin condition, that’s a red flag. And if the caregiver in the room is overwhelmed or frustrated by having to put cream on twice a day, I’ll use this to advance treatment.
What resources are available for dermatologists interested in improving their geriatric dermatology skills or advancing the area?
For those interested in investigating these issues or improving their practices, the AAD’s Geriatric Dermatology ERG is always welcoming of new members. The ERG will have an all-inclusive meeting at the 2025 annual AAD meeting in March.
The AAD also has educational modules on geriatric dermatology that were recently published as an initiative of our ERG. More information is available on the website. Also valuable is the ElderDerm conference hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC; the second such conference takes place in May 2025.
Butler reported that he had no relevant financial disclosures.
A version of this article appeared on Medscape.com.
Why Do People Struggle to Prioritize Their Long-Term Health?
Understanding how people make health-related decisions requires a deeper exploration of their motivations, beliefs, and circumstances, Christopher Dye, DPhil, professor of epidemiology at the University of Oxford in England, and former director of strategy at the World Health Organization, said in an interview. “In public health, we tend to prescribe solutions. But unless we understand how people really make choices about health and why they are less interested in prevention and happier to wait until they become ill, then we are not in the position to shift away from curative treatments to preventive treatments.”
Despite the well-documented benefits of preventive measures, many people fail to engage in proactive health behaviors. This can be attributed to psychological biases and socioeconomic factors that shape how people prioritize their health.
“The choices people make have some to do with facts, but they also have much to do with values and perception. We need to understand and take these perceptions and values seriously,” Dye said.
The Paradox of Prevention
People often recognize prevention as the right course of action but fail to act. “We know it’s the right thing to do, but we don’t do it,” Dye said.
He explained that, when considering potential future threats, we assess two key factors: The severity of the danger and the cost of addressing it. Action is more likely when the danger is significant and the cost of mitigation is low.
This dynamic can be broken down into three critical questions:
What is the nature of the hazard? Is the threat severe, like Ebola, which has a case fatality rate of around 50% in untreated cases, or relatively milder, like COVID-19, with a fatality rate of less than 1% but a much broader spread? The nastier the hazard, the more likely we are to take it seriously.
How likely is it to happen? Even a severe threat will not prompt much concern if its likelihood is perceived as low. Our willingness to act depends heavily on how probable people think the hazard is.
When is it likely to happen? A threat looming in the immediate future is more compelling than one projected weeks, months, or years away. This is because people tend to heavily discount the value of future risks.
When these factors — severity, likelihood, and immediacy — combine with low mitigation costs, the incentives for action align.
However, cost is not limited to financial expense. It encompasses effort, willpower, access to information, and personal inclination. Similarly, the perception of threat is shaped not just by hard data and epidemiology but also by subjective values and cultural interpretations.
“We place a high value on now rather than later,” Theresa Marteau, PhD, a psychologist and behavioral scientist and director of the Behaviour and Health Research Unit at the University of Cambridge in England, said in an interview. “Treatment is about fixing a problem that we have now, rather than trying to avoid a problem sometime in the future. We also place a high value on certainty: I’m ill today, and I want to avoid that, as opposed to putting resources on a possible disease that might or might not occur.”
Investing in the Future: A Privilege of Stability
People often undervalue future health risks because of temporal discounting, a cognitive bias where immediate rewards are prioritized over long-term benefits. This tendency makes it challenging to address health issues that may only manifest years later.
From a public health perspective, this creates challenges. Warning individuals that harmful behaviors, such as smoking, may lead to severe health problems in a decade often falls on deaf ears. People naturally focus on immediate concerns, particularly when grappling with present challenges. For those living in poverty or social instability, the urgency of daily survival frequently outweighs the perceived benefits of preventive health measures.
“A cigarette during the day is just one brief source of pleasure, a short-term escape from all the other stuff happening in their lives, and there’s more of that stuff happening to poorer people than there is to richer people,” Dye said.
He said that long-term thinking comes more naturally to those with stability and resources. People who are financially secure, have stable jobs, supportive families, and comfortable homes are better equipped to invest for the future and prioritize their health.
“People value their health regardless of their social and economic circumstances,” said Marteau. “But they might not have the resources to engage in behavior-changing activities.”
Bringing the Future to the Present
Effective interventions often involve a combination of “sticks” (deterrents) and “carrots” (rewards), Dye explained. Both approaches aim to bridge the gap between immediate actions and future benefits by making preventive behaviors more appealing in the short term. “We need to bring the future into the present,” he added.
Raising the cost of unhealthy behaviors has proven effective. For example, increasing the price of cigarettes leads to significant reductions in smoking rates. When smoking becomes less affordable, individuals are more likely to quit. Dye said that this approach works to a certain extent. At some point, the number of people quitting plateaus and those from low socioeconomic backgrounds are those more likely to continue to smoke.
Offering immediate rewards for preventive behaviors provides a powerful incentive. Things that give tangible benefits, like attending regular health checkups, receiving vaccinations, or joining fitness programs, can motivate individuals to engage in health-preserving activities. “The key is ensuring these benefits are timely and meaningful, as delayed rewards are less effective in overcoming the natural bias toward the present,” said Dye.
Healthcare providers are best placed to help people engage in preventive behavior by referring patients to the right services, such as programs to stop smoking, weight loss programs and medications, or mental health providers, Marteau said. “It’s not telling people to stop smoking or change their diet. It’s about signposting them to effective services that will help them change their behavior.”
Dye and Marteau reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Understanding how people make health-related decisions requires a deeper exploration of their motivations, beliefs, and circumstances, Christopher Dye, DPhil, professor of epidemiology at the University of Oxford in England, and former director of strategy at the World Health Organization, said in an interview. “In public health, we tend to prescribe solutions. But unless we understand how people really make choices about health and why they are less interested in prevention and happier to wait until they become ill, then we are not in the position to shift away from curative treatments to preventive treatments.”
Despite the well-documented benefits of preventive measures, many people fail to engage in proactive health behaviors. This can be attributed to psychological biases and socioeconomic factors that shape how people prioritize their health.
“The choices people make have some to do with facts, but they also have much to do with values and perception. We need to understand and take these perceptions and values seriously,” Dye said.
The Paradox of Prevention
People often recognize prevention as the right course of action but fail to act. “We know it’s the right thing to do, but we don’t do it,” Dye said.
He explained that, when considering potential future threats, we assess two key factors: The severity of the danger and the cost of addressing it. Action is more likely when the danger is significant and the cost of mitigation is low.
This dynamic can be broken down into three critical questions:
What is the nature of the hazard? Is the threat severe, like Ebola, which has a case fatality rate of around 50% in untreated cases, or relatively milder, like COVID-19, with a fatality rate of less than 1% but a much broader spread? The nastier the hazard, the more likely we are to take it seriously.
How likely is it to happen? Even a severe threat will not prompt much concern if its likelihood is perceived as low. Our willingness to act depends heavily on how probable people think the hazard is.
When is it likely to happen? A threat looming in the immediate future is more compelling than one projected weeks, months, or years away. This is because people tend to heavily discount the value of future risks.
When these factors — severity, likelihood, and immediacy — combine with low mitigation costs, the incentives for action align.
However, cost is not limited to financial expense. It encompasses effort, willpower, access to information, and personal inclination. Similarly, the perception of threat is shaped not just by hard data and epidemiology but also by subjective values and cultural interpretations.
“We place a high value on now rather than later,” Theresa Marteau, PhD, a psychologist and behavioral scientist and director of the Behaviour and Health Research Unit at the University of Cambridge in England, said in an interview. “Treatment is about fixing a problem that we have now, rather than trying to avoid a problem sometime in the future. We also place a high value on certainty: I’m ill today, and I want to avoid that, as opposed to putting resources on a possible disease that might or might not occur.”
Investing in the Future: A Privilege of Stability
People often undervalue future health risks because of temporal discounting, a cognitive bias where immediate rewards are prioritized over long-term benefits. This tendency makes it challenging to address health issues that may only manifest years later.
From a public health perspective, this creates challenges. Warning individuals that harmful behaviors, such as smoking, may lead to severe health problems in a decade often falls on deaf ears. People naturally focus on immediate concerns, particularly when grappling with present challenges. For those living in poverty or social instability, the urgency of daily survival frequently outweighs the perceived benefits of preventive health measures.
“A cigarette during the day is just one brief source of pleasure, a short-term escape from all the other stuff happening in their lives, and there’s more of that stuff happening to poorer people than there is to richer people,” Dye said.
He said that long-term thinking comes more naturally to those with stability and resources. People who are financially secure, have stable jobs, supportive families, and comfortable homes are better equipped to invest for the future and prioritize their health.
“People value their health regardless of their social and economic circumstances,” said Marteau. “But they might not have the resources to engage in behavior-changing activities.”
Bringing the Future to the Present
Effective interventions often involve a combination of “sticks” (deterrents) and “carrots” (rewards), Dye explained. Both approaches aim to bridge the gap between immediate actions and future benefits by making preventive behaviors more appealing in the short term. “We need to bring the future into the present,” he added.
Raising the cost of unhealthy behaviors has proven effective. For example, increasing the price of cigarettes leads to significant reductions in smoking rates. When smoking becomes less affordable, individuals are more likely to quit. Dye said that this approach works to a certain extent. At some point, the number of people quitting plateaus and those from low socioeconomic backgrounds are those more likely to continue to smoke.
Offering immediate rewards for preventive behaviors provides a powerful incentive. Things that give tangible benefits, like attending regular health checkups, receiving vaccinations, or joining fitness programs, can motivate individuals to engage in health-preserving activities. “The key is ensuring these benefits are timely and meaningful, as delayed rewards are less effective in overcoming the natural bias toward the present,” said Dye.
Healthcare providers are best placed to help people engage in preventive behavior by referring patients to the right services, such as programs to stop smoking, weight loss programs and medications, or mental health providers, Marteau said. “It’s not telling people to stop smoking or change their diet. It’s about signposting them to effective services that will help them change their behavior.”
Dye and Marteau reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Understanding how people make health-related decisions requires a deeper exploration of their motivations, beliefs, and circumstances, Christopher Dye, DPhil, professor of epidemiology at the University of Oxford in England, and former director of strategy at the World Health Organization, said in an interview. “In public health, we tend to prescribe solutions. But unless we understand how people really make choices about health and why they are less interested in prevention and happier to wait until they become ill, then we are not in the position to shift away from curative treatments to preventive treatments.”
Despite the well-documented benefits of preventive measures, many people fail to engage in proactive health behaviors. This can be attributed to psychological biases and socioeconomic factors that shape how people prioritize their health.
“The choices people make have some to do with facts, but they also have much to do with values and perception. We need to understand and take these perceptions and values seriously,” Dye said.
The Paradox of Prevention
People often recognize prevention as the right course of action but fail to act. “We know it’s the right thing to do, but we don’t do it,” Dye said.
He explained that, when considering potential future threats, we assess two key factors: The severity of the danger and the cost of addressing it. Action is more likely when the danger is significant and the cost of mitigation is low.
This dynamic can be broken down into three critical questions:
What is the nature of the hazard? Is the threat severe, like Ebola, which has a case fatality rate of around 50% in untreated cases, or relatively milder, like COVID-19, with a fatality rate of less than 1% but a much broader spread? The nastier the hazard, the more likely we are to take it seriously.
How likely is it to happen? Even a severe threat will not prompt much concern if its likelihood is perceived as low. Our willingness to act depends heavily on how probable people think the hazard is.
When is it likely to happen? A threat looming in the immediate future is more compelling than one projected weeks, months, or years away. This is because people tend to heavily discount the value of future risks.
When these factors — severity, likelihood, and immediacy — combine with low mitigation costs, the incentives for action align.
However, cost is not limited to financial expense. It encompasses effort, willpower, access to information, and personal inclination. Similarly, the perception of threat is shaped not just by hard data and epidemiology but also by subjective values and cultural interpretations.
“We place a high value on now rather than later,” Theresa Marteau, PhD, a psychologist and behavioral scientist and director of the Behaviour and Health Research Unit at the University of Cambridge in England, said in an interview. “Treatment is about fixing a problem that we have now, rather than trying to avoid a problem sometime in the future. We also place a high value on certainty: I’m ill today, and I want to avoid that, as opposed to putting resources on a possible disease that might or might not occur.”
Investing in the Future: A Privilege of Stability
People often undervalue future health risks because of temporal discounting, a cognitive bias where immediate rewards are prioritized over long-term benefits. This tendency makes it challenging to address health issues that may only manifest years later.
From a public health perspective, this creates challenges. Warning individuals that harmful behaviors, such as smoking, may lead to severe health problems in a decade often falls on deaf ears. People naturally focus on immediate concerns, particularly when grappling with present challenges. For those living in poverty or social instability, the urgency of daily survival frequently outweighs the perceived benefits of preventive health measures.
“A cigarette during the day is just one brief source of pleasure, a short-term escape from all the other stuff happening in their lives, and there’s more of that stuff happening to poorer people than there is to richer people,” Dye said.
He said that long-term thinking comes more naturally to those with stability and resources. People who are financially secure, have stable jobs, supportive families, and comfortable homes are better equipped to invest for the future and prioritize their health.
“People value their health regardless of their social and economic circumstances,” said Marteau. “But they might not have the resources to engage in behavior-changing activities.”
Bringing the Future to the Present
Effective interventions often involve a combination of “sticks” (deterrents) and “carrots” (rewards), Dye explained. Both approaches aim to bridge the gap between immediate actions and future benefits by making preventive behaviors more appealing in the short term. “We need to bring the future into the present,” he added.
Raising the cost of unhealthy behaviors has proven effective. For example, increasing the price of cigarettes leads to significant reductions in smoking rates. When smoking becomes less affordable, individuals are more likely to quit. Dye said that this approach works to a certain extent. At some point, the number of people quitting plateaus and those from low socioeconomic backgrounds are those more likely to continue to smoke.
Offering immediate rewards for preventive behaviors provides a powerful incentive. Things that give tangible benefits, like attending regular health checkups, receiving vaccinations, or joining fitness programs, can motivate individuals to engage in health-preserving activities. “The key is ensuring these benefits are timely and meaningful, as delayed rewards are less effective in overcoming the natural bias toward the present,” said Dye.
Healthcare providers are best placed to help people engage in preventive behavior by referring patients to the right services, such as programs to stop smoking, weight loss programs and medications, or mental health providers, Marteau said. “It’s not telling people to stop smoking or change their diet. It’s about signposting them to effective services that will help them change their behavior.”
Dye and Marteau reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA Approves Durvalumab for Limited-Stage SCLC
The Food and Drug Administration approval makes the monoclonal antibody — which is already approved for multiple tumor types — the first immunotherapy regimen approved in this setting, AstraZeneca noted in a press release.
“Durvalumab is the first and only systemic treatment following curative-intent, platinum-based chemoradiotherapy to show improved survival for patients with this aggressive form of lung cancer,” international coordinating investigator on the trial, Suresh Senan, PhD, stated in the press release. “This finding represents the first advance for this disease in 4 decades.”
Approval, which followed Priority Review and Breakthrough Therapy Designation, was based on findings from the phase 3 ADRIATIC trial showing a 27% reduction in the risk for death with durvalumab vs placebo.
Findings from the trial were reported during a plenary session at the 2024 American Society of Clinical Oncology conference, and subsequently published in The New England Journal of Medicine.
In 730 patients with LS-SCLC who were randomized 1:1:1 to receive single-agent durvalumab, durvalumab in combination with tremelimumab, or placebo, overall survival (OS) and progression-free survival (PFS) were significantly improved with durvalumab alone vs placebo (hazard ratio, 0.73 and 0.76, for OS and PFS, respectively). Median OS was 55.9 months vs 33.4 months with durvalumab vs placebo, and PFS was 16.6 vs 9.2 months, respectively.
Senan, a professor of clinical experimental radiotherapy at the Amsterdam University Medical Center in the Netherlands, noted in the press release that 57% of patients were still alive at 3 years after being treated with durvalumab, which underscores the practice-changing potential of this medicine in this setting.
“This new treatment option is a game changer for patients with limited-stage small cell lung cancer, a disease known for its high rate of recurrence,” Dusty Donaldson, founder and executive director of the nonprofit advocacy organization LiveLung, stated in the release. “Historically, more often than not, clinical trials to identify new treatment options for this type of cancer have failed to show benefit. We are therefore so excited that many more people will now have the opportunity to access this immunotherapy treatment that holds the potential to significantly improve outcomes.”
Adverse reactions occurring in at least 20% of patients in the ADRIATIC trial included pneumonitis or radiation pneumonitis and fatigue.
The recommended durvalumab dose, according to prescribing information, is 1500 mg every 4 weeks for patients weighing at least 30 kg and 20 mg/kg every 4 weeks for those weighing less than 30 kg, until disease progression or unacceptable toxicity or a maximum of 24 months.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration approval makes the monoclonal antibody — which is already approved for multiple tumor types — the first immunotherapy regimen approved in this setting, AstraZeneca noted in a press release.
“Durvalumab is the first and only systemic treatment following curative-intent, platinum-based chemoradiotherapy to show improved survival for patients with this aggressive form of lung cancer,” international coordinating investigator on the trial, Suresh Senan, PhD, stated in the press release. “This finding represents the first advance for this disease in 4 decades.”
Approval, which followed Priority Review and Breakthrough Therapy Designation, was based on findings from the phase 3 ADRIATIC trial showing a 27% reduction in the risk for death with durvalumab vs placebo.
Findings from the trial were reported during a plenary session at the 2024 American Society of Clinical Oncology conference, and subsequently published in The New England Journal of Medicine.
In 730 patients with LS-SCLC who were randomized 1:1:1 to receive single-agent durvalumab, durvalumab in combination with tremelimumab, or placebo, overall survival (OS) and progression-free survival (PFS) were significantly improved with durvalumab alone vs placebo (hazard ratio, 0.73 and 0.76, for OS and PFS, respectively). Median OS was 55.9 months vs 33.4 months with durvalumab vs placebo, and PFS was 16.6 vs 9.2 months, respectively.
Senan, a professor of clinical experimental radiotherapy at the Amsterdam University Medical Center in the Netherlands, noted in the press release that 57% of patients were still alive at 3 years after being treated with durvalumab, which underscores the practice-changing potential of this medicine in this setting.
“This new treatment option is a game changer for patients with limited-stage small cell lung cancer, a disease known for its high rate of recurrence,” Dusty Donaldson, founder and executive director of the nonprofit advocacy organization LiveLung, stated in the release. “Historically, more often than not, clinical trials to identify new treatment options for this type of cancer have failed to show benefit. We are therefore so excited that many more people will now have the opportunity to access this immunotherapy treatment that holds the potential to significantly improve outcomes.”
Adverse reactions occurring in at least 20% of patients in the ADRIATIC trial included pneumonitis or radiation pneumonitis and fatigue.
The recommended durvalumab dose, according to prescribing information, is 1500 mg every 4 weeks for patients weighing at least 30 kg and 20 mg/kg every 4 weeks for those weighing less than 30 kg, until disease progression or unacceptable toxicity or a maximum of 24 months.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration approval makes the monoclonal antibody — which is already approved for multiple tumor types — the first immunotherapy regimen approved in this setting, AstraZeneca noted in a press release.
“Durvalumab is the first and only systemic treatment following curative-intent, platinum-based chemoradiotherapy to show improved survival for patients with this aggressive form of lung cancer,” international coordinating investigator on the trial, Suresh Senan, PhD, stated in the press release. “This finding represents the first advance for this disease in 4 decades.”
Approval, which followed Priority Review and Breakthrough Therapy Designation, was based on findings from the phase 3 ADRIATIC trial showing a 27% reduction in the risk for death with durvalumab vs placebo.
Findings from the trial were reported during a plenary session at the 2024 American Society of Clinical Oncology conference, and subsequently published in The New England Journal of Medicine.
In 730 patients with LS-SCLC who were randomized 1:1:1 to receive single-agent durvalumab, durvalumab in combination with tremelimumab, or placebo, overall survival (OS) and progression-free survival (PFS) were significantly improved with durvalumab alone vs placebo (hazard ratio, 0.73 and 0.76, for OS and PFS, respectively). Median OS was 55.9 months vs 33.4 months with durvalumab vs placebo, and PFS was 16.6 vs 9.2 months, respectively.
Senan, a professor of clinical experimental radiotherapy at the Amsterdam University Medical Center in the Netherlands, noted in the press release that 57% of patients were still alive at 3 years after being treated with durvalumab, which underscores the practice-changing potential of this medicine in this setting.
“This new treatment option is a game changer for patients with limited-stage small cell lung cancer, a disease known for its high rate of recurrence,” Dusty Donaldson, founder and executive director of the nonprofit advocacy organization LiveLung, stated in the release. “Historically, more often than not, clinical trials to identify new treatment options for this type of cancer have failed to show benefit. We are therefore so excited that many more people will now have the opportunity to access this immunotherapy treatment that holds the potential to significantly improve outcomes.”
Adverse reactions occurring in at least 20% of patients in the ADRIATIC trial included pneumonitis or radiation pneumonitis and fatigue.
The recommended durvalumab dose, according to prescribing information, is 1500 mg every 4 weeks for patients weighing at least 30 kg and 20 mg/kg every 4 weeks for those weighing less than 30 kg, until disease progression or unacceptable toxicity or a maximum of 24 months.
A version of this article first appeared on Medscape.com.
New Cancer Vaccines on the Horizon: Renewed Hope or Hype?
Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.
But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.
Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.
In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.
said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.
“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.
Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.
“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”
Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.
Then: Where We Were
Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.
In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.
Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”
In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”
Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.
In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.
In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.
That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.
In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.
And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.
But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.
When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.
But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.
Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.
“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”
A Turning Point?
Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.
Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.
Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.
Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.
Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.
“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.”
Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.
One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.
But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”
“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”
Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.
“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”
Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.
As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”
A version of this article first appeared on Medscape.com.
Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.
But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.
Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.
In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.
said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.
“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.
Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.
“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”
Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.
Then: Where We Were
Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.
In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.
Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”
In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”
Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.
In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.
In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.
That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.
In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.
And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.
But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.
When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.
But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.
Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.
“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”
A Turning Point?
Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.
Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.
Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.
Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.
Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.
“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.”
Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.
One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.
But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”
“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”
Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.
“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”
Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.
As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”
A version of this article first appeared on Medscape.com.
Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.
But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.
Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.
In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.
said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.
“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.
Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.
“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”
Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.
Then: Where We Were
Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.
In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.
Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”
In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”
Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.
In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.
In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.
That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.
In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.
And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.
But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.
When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.
But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.
Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.
“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”
A Turning Point?
Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.
Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.
Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.
Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.
Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.
“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.”
Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.
One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.
But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”
“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”
Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.
“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”
Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.
As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”
A version of this article first appeared on Medscape.com.
FDA Approves Bizengri for NSCLC and Pancreatic Cancers Harboring NRG1 Gene Fusion
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Has Tirzepatide Scaled the HFpEF/Obesity SUMMIT?
The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.
Known Facts About HFpEF
HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.
Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.
GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.
This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.
The SUMMIT Trial
The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.
Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.
Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.
Tirzepatide Results
The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).
The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).
The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).
The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.
Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).
Authors’ Conclusions and Expert Comments
At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.
Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”
Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.
The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.
My Six Concerns With SUMMIT
The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.
The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.
I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.
The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.
The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.
For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.
The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.
Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.
The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.
Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.
In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.
Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.
Known Facts About HFpEF
HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.
Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.
GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.
This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.
The SUMMIT Trial
The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.
Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.
Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.
Tirzepatide Results
The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).
The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).
The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).
The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.
Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).
Authors’ Conclusions and Expert Comments
At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.
Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”
Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.
The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.
My Six Concerns With SUMMIT
The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.
The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.
I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.
The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.
The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.
For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.
The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.
Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.
The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.
Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.
In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.
Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.
Known Facts About HFpEF
HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.
Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.
GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.
This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.
The SUMMIT Trial
The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.
Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.
Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.
Tirzepatide Results
The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).
The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).
The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).
The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.
Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).
Authors’ Conclusions and Expert Comments
At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.
Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”
Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.
The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.
My Six Concerns With SUMMIT
The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.
The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.
I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.
The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.
The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.
For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.
The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.
Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.
The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.
Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.
In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.
Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
GLP-1s Hold Promise for Addiction but Questions Remain
Glucagon-like peptide 1 receptor agonist (GLP-1) prescriptions for diabetes and obesity treatment are soaring, as is the interest in their potential for treating an array of other conditions. One area in particular is addiction, which, like obesity and diabetes, has been increasing, both in terms of case numbers and deaths from drug overdose, excessive alcohol use, and tobacco/e-cigarettes.
“The evidence is very preliminary and very exciting,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse (NIDA). “The studies have been going on for more than a decade looking at the effects of GLP medications, mostly first generation and predominantly in rodents,” she said.
GLP “drugs like exenatide and liraglutide all reduced consumption of nicotine, of alcohol, of cocaine, and response to opioids,” Volkow said.
Clinical, Real-World Data Promising
Second-generation agents like semaglutide appear to hold greater promise than their first-generation counterparts. Volkow noted that not only is semaglutide a “much more potent drug,” but pointed to recent findings that saw significant declines in heavy drinking days among patients with alcohol use disorder (AUD).
At the Research Society on Alcohol’s annual meeting in June, researchers from the University of North Carolina at Chapel Hill presented findings of a 2-month, phase 2, randomized clinical trial comparing two low doses (0.25 mg/wk, 0.5 mg/wk) of semaglutide with placebo in 48 participants reporting symptoms of AUD. Though preliminary and unpublished, the data showed a reduction in drinking quantity and heavy drinking in the semaglutide vs placebo groups.
Real-world evidence from electronic health records has also underscored the potential benefit of semaglutide in AUD. In a 12-month retrospective cohort analysis of the records of patients with obesity and no prior AUD diagnosis prescribed semaglutide (n = 45,797) or non-GLP-1 anti-obesity medications (naltrexone, topiramate, n = 38,028), semaglutide was associated with a 50% lower risk for a recurrent AUD diagnosis and a 56% significantly lower risk for incidence AUD diagnosis across gender, age group, and race, and in patients with/without type 2 diabetes.
Likewise, findings from another cohort analysis assigned 1306 treatment-naive patients with type 2 diabetes and no prior AUD diagnosis to semaglutide or non-GLP-1 anti-diabetes medications and followed them for 12 months. Compared with people prescribed non-GLP-1 diabetes medications, those who took semaglutide had a 42% lower risk for recurrent alcohol use diagnosis, consistent across gender, age group, and race, whether the person had been diagnosed with obesity.
However, AUD is not the only addiction where semaglutide appears to have potential benefit. Cohort studies conducted by Volkow and her colleagues have suggested as much as a 78% reduced risk or opioid overdose in patients with comorbid obesity and type 2 diabetes) and a 44% reduction in cannabis use disorder in type 2 diabetes patients without a prior cannabis use disorder history.
Unclear Mechanisms, Multiple Theories
It’s not entirely clear how semaglutide provides a path for addicts to reduce their cravings or which patients might benefit most.
Preclinical studies have suggested that GLP-1 receptors are expressed throughout the mesolimbic dopamine system and transmit dopamine directly to reward centers in the forebrain, for example, the nucleus accumbens. The drugs appear to reduce dopamine release and transmission to these reward centers, as well as to areas that are responsible for impulse control.
“What we’re seeing is counteracting mechanisms that allow you to self-regulate are also involved in addiction, but I don’t know to what extent these medications could help strengthen that,” said Volkow.
Henry Kranzler, MD, professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, has a paper in press looking at genetic correlation between body mass index (BMI) and AUD. “Genetic analysis showed that many of the same genes are working in both disorders but in opposite directions,” he said.
The bottom line is that “they share genetics, but by no means are they the same; this gives us reason to believe that the GLP-1s could be beneficial in obesity but not nearly as beneficial for treating addiction,” said Kranzler.
Behind Closed Doors
Like many people with overweight or obesity who are on semaglutide, Bridget Pilloud, a writer who divides her time between Washington State and Arizona, no longer has any desire to drink.
“I used to really enjoy sitting and slowly sipping an Old Fashioned. I used to really enjoy specific whiskeys. Now, I don’t even like the flavor; the pleasure of drinking is gone,” she said.
Inexplicably, Pilloud said that she’s also given up compulsive shopping; “The hunt and acquisition of it was always really delicious to me,” she said.
Pilloud’s experience is not unique. Angela Fitch, MD, an obesity medicine specialist, co-founder and CMO of knownwell health, and former president of the Obesity Medicine Association, has had patients on semaglutide tell her that they’re not shopping as much.
But self-reports about alcohol consumption are far more common.
A 2023 analysis of social media posts reinforced that the experience is quite common, albeit self-reported.
Researchers used machine learning attribution mapping of 68,250 posts related to GLP-1 or GLP-1/glucose-dependent insulinotropic polypeptide agonists on the Reddit platform. Among the 1580 alcohol-related posts, 71% (1134/1580) of users of either drug said they had reduced cravings and decreased desire to drink. In a remote companion study of 153 people with obesity taking semaglutide (n = 56), tirzepatide (n = 50), or neither (n = 47), there appeared to be a reduced suppression of the desire to consume alcohol, with users reporting fewer drinks and binge episodes than control individuals.
Self-reports also underscored the association between either of the medications and less stimulating/sedative effects of alcohol compared with before starting the medications and to controls.
Behind closed doors, there appears to be as much chatter about the potential of these agents for AUD and other addiction disorders as there are questions about factors like treatment duration, safety of long-term, chronic use, and dosage.
“We don’t have data around people with normal weight and how much risk that is to them if they start taking these medications for addiction and reduce their BMI as low as 18,” said Fitch.
There’s also the question of when and how to wean patients off the medications, a consideration that is quite important for patients with addiction problems, said Volkow.
“What happens when you become addicted to drugs is that you start to degrade social support systems needed for well-being,” she explained. “The big difference with drugs versus foods is that you can live happily with no drugs at all, whereas you die if you don’t eat. So, there are greater challenges in the ability to change the environment (eg, help stabilize everyday life so people have alternative reinforcers) when you remove the reward.”
Additional considerations range from overuse and the development of treatment-resistant obesity to the need to ensure that patients on these drugs receive ongoing management and, of course, access, noted Fitch.
Still, the NIDA coffers are open. “We’re waiting for proposals,” said Volkow.
Fitch is cofounder and CMO of knownwell health. Volkow reported no relevant financial relationships. Kranzler is a member of advisory boards for Altimmune, Clearmind Medicine, Dicerna Pharmaceuticals, Enthion Pharmaceuticals, Eli Lilly and Company, and Sophrosyne Pharmaceuticals; a consultant to Sobrera Pharma and Altimmune; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the past 3 years by Alkermes, Dicerna Pharmaceuticals, Ethypharm, Imbrium, Indivior, Kinnov, Eli Lilly, Otsuka, and Pear; and a holder of US patent 10,900,082 titled: “Genotype-guided dosing of opioid agonists,” issued on January 26, 2021.
A version of this article appeared on Medscape.com.
Glucagon-like peptide 1 receptor agonist (GLP-1) prescriptions for diabetes and obesity treatment are soaring, as is the interest in their potential for treating an array of other conditions. One area in particular is addiction, which, like obesity and diabetes, has been increasing, both in terms of case numbers and deaths from drug overdose, excessive alcohol use, and tobacco/e-cigarettes.
“The evidence is very preliminary and very exciting,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse (NIDA). “The studies have been going on for more than a decade looking at the effects of GLP medications, mostly first generation and predominantly in rodents,” she said.
GLP “drugs like exenatide and liraglutide all reduced consumption of nicotine, of alcohol, of cocaine, and response to opioids,” Volkow said.
Clinical, Real-World Data Promising
Second-generation agents like semaglutide appear to hold greater promise than their first-generation counterparts. Volkow noted that not only is semaglutide a “much more potent drug,” but pointed to recent findings that saw significant declines in heavy drinking days among patients with alcohol use disorder (AUD).
At the Research Society on Alcohol’s annual meeting in June, researchers from the University of North Carolina at Chapel Hill presented findings of a 2-month, phase 2, randomized clinical trial comparing two low doses (0.25 mg/wk, 0.5 mg/wk) of semaglutide with placebo in 48 participants reporting symptoms of AUD. Though preliminary and unpublished, the data showed a reduction in drinking quantity and heavy drinking in the semaglutide vs placebo groups.
Real-world evidence from electronic health records has also underscored the potential benefit of semaglutide in AUD. In a 12-month retrospective cohort analysis of the records of patients with obesity and no prior AUD diagnosis prescribed semaglutide (n = 45,797) or non-GLP-1 anti-obesity medications (naltrexone, topiramate, n = 38,028), semaglutide was associated with a 50% lower risk for a recurrent AUD diagnosis and a 56% significantly lower risk for incidence AUD diagnosis across gender, age group, and race, and in patients with/without type 2 diabetes.
Likewise, findings from another cohort analysis assigned 1306 treatment-naive patients with type 2 diabetes and no prior AUD diagnosis to semaglutide or non-GLP-1 anti-diabetes medications and followed them for 12 months. Compared with people prescribed non-GLP-1 diabetes medications, those who took semaglutide had a 42% lower risk for recurrent alcohol use diagnosis, consistent across gender, age group, and race, whether the person had been diagnosed with obesity.
However, AUD is not the only addiction where semaglutide appears to have potential benefit. Cohort studies conducted by Volkow and her colleagues have suggested as much as a 78% reduced risk or opioid overdose in patients with comorbid obesity and type 2 diabetes) and a 44% reduction in cannabis use disorder in type 2 diabetes patients without a prior cannabis use disorder history.
Unclear Mechanisms, Multiple Theories
It’s not entirely clear how semaglutide provides a path for addicts to reduce their cravings or which patients might benefit most.
Preclinical studies have suggested that GLP-1 receptors are expressed throughout the mesolimbic dopamine system and transmit dopamine directly to reward centers in the forebrain, for example, the nucleus accumbens. The drugs appear to reduce dopamine release and transmission to these reward centers, as well as to areas that are responsible for impulse control.
“What we’re seeing is counteracting mechanisms that allow you to self-regulate are also involved in addiction, but I don’t know to what extent these medications could help strengthen that,” said Volkow.
Henry Kranzler, MD, professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, has a paper in press looking at genetic correlation between body mass index (BMI) and AUD. “Genetic analysis showed that many of the same genes are working in both disorders but in opposite directions,” he said.
The bottom line is that “they share genetics, but by no means are they the same; this gives us reason to believe that the GLP-1s could be beneficial in obesity but not nearly as beneficial for treating addiction,” said Kranzler.
Behind Closed Doors
Like many people with overweight or obesity who are on semaglutide, Bridget Pilloud, a writer who divides her time between Washington State and Arizona, no longer has any desire to drink.
“I used to really enjoy sitting and slowly sipping an Old Fashioned. I used to really enjoy specific whiskeys. Now, I don’t even like the flavor; the pleasure of drinking is gone,” she said.
Inexplicably, Pilloud said that she’s also given up compulsive shopping; “The hunt and acquisition of it was always really delicious to me,” she said.
Pilloud’s experience is not unique. Angela Fitch, MD, an obesity medicine specialist, co-founder and CMO of knownwell health, and former president of the Obesity Medicine Association, has had patients on semaglutide tell her that they’re not shopping as much.
But self-reports about alcohol consumption are far more common.
A 2023 analysis of social media posts reinforced that the experience is quite common, albeit self-reported.
Researchers used machine learning attribution mapping of 68,250 posts related to GLP-1 or GLP-1/glucose-dependent insulinotropic polypeptide agonists on the Reddit platform. Among the 1580 alcohol-related posts, 71% (1134/1580) of users of either drug said they had reduced cravings and decreased desire to drink. In a remote companion study of 153 people with obesity taking semaglutide (n = 56), tirzepatide (n = 50), or neither (n = 47), there appeared to be a reduced suppression of the desire to consume alcohol, with users reporting fewer drinks and binge episodes than control individuals.
Self-reports also underscored the association between either of the medications and less stimulating/sedative effects of alcohol compared with before starting the medications and to controls.
Behind closed doors, there appears to be as much chatter about the potential of these agents for AUD and other addiction disorders as there are questions about factors like treatment duration, safety of long-term, chronic use, and dosage.
“We don’t have data around people with normal weight and how much risk that is to them if they start taking these medications for addiction and reduce their BMI as low as 18,” said Fitch.
There’s also the question of when and how to wean patients off the medications, a consideration that is quite important for patients with addiction problems, said Volkow.
“What happens when you become addicted to drugs is that you start to degrade social support systems needed for well-being,” she explained. “The big difference with drugs versus foods is that you can live happily with no drugs at all, whereas you die if you don’t eat. So, there are greater challenges in the ability to change the environment (eg, help stabilize everyday life so people have alternative reinforcers) when you remove the reward.”
Additional considerations range from overuse and the development of treatment-resistant obesity to the need to ensure that patients on these drugs receive ongoing management and, of course, access, noted Fitch.
Still, the NIDA coffers are open. “We’re waiting for proposals,” said Volkow.
Fitch is cofounder and CMO of knownwell health. Volkow reported no relevant financial relationships. Kranzler is a member of advisory boards for Altimmune, Clearmind Medicine, Dicerna Pharmaceuticals, Enthion Pharmaceuticals, Eli Lilly and Company, and Sophrosyne Pharmaceuticals; a consultant to Sobrera Pharma and Altimmune; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the past 3 years by Alkermes, Dicerna Pharmaceuticals, Ethypharm, Imbrium, Indivior, Kinnov, Eli Lilly, Otsuka, and Pear; and a holder of US patent 10,900,082 titled: “Genotype-guided dosing of opioid agonists,” issued on January 26, 2021.
A version of this article appeared on Medscape.com.
Glucagon-like peptide 1 receptor agonist (GLP-1) prescriptions for diabetes and obesity treatment are soaring, as is the interest in their potential for treating an array of other conditions. One area in particular is addiction, which, like obesity and diabetes, has been increasing, both in terms of case numbers and deaths from drug overdose, excessive alcohol use, and tobacco/e-cigarettes.
“The evidence is very preliminary and very exciting,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse (NIDA). “The studies have been going on for more than a decade looking at the effects of GLP medications, mostly first generation and predominantly in rodents,” she said.
GLP “drugs like exenatide and liraglutide all reduced consumption of nicotine, of alcohol, of cocaine, and response to opioids,” Volkow said.
Clinical, Real-World Data Promising
Second-generation agents like semaglutide appear to hold greater promise than their first-generation counterparts. Volkow noted that not only is semaglutide a “much more potent drug,” but pointed to recent findings that saw significant declines in heavy drinking days among patients with alcohol use disorder (AUD).
At the Research Society on Alcohol’s annual meeting in June, researchers from the University of North Carolina at Chapel Hill presented findings of a 2-month, phase 2, randomized clinical trial comparing two low doses (0.25 mg/wk, 0.5 mg/wk) of semaglutide with placebo in 48 participants reporting symptoms of AUD. Though preliminary and unpublished, the data showed a reduction in drinking quantity and heavy drinking in the semaglutide vs placebo groups.
Real-world evidence from electronic health records has also underscored the potential benefit of semaglutide in AUD. In a 12-month retrospective cohort analysis of the records of patients with obesity and no prior AUD diagnosis prescribed semaglutide (n = 45,797) or non-GLP-1 anti-obesity medications (naltrexone, topiramate, n = 38,028), semaglutide was associated with a 50% lower risk for a recurrent AUD diagnosis and a 56% significantly lower risk for incidence AUD diagnosis across gender, age group, and race, and in patients with/without type 2 diabetes.
Likewise, findings from another cohort analysis assigned 1306 treatment-naive patients with type 2 diabetes and no prior AUD diagnosis to semaglutide or non-GLP-1 anti-diabetes medications and followed them for 12 months. Compared with people prescribed non-GLP-1 diabetes medications, those who took semaglutide had a 42% lower risk for recurrent alcohol use diagnosis, consistent across gender, age group, and race, whether the person had been diagnosed with obesity.
However, AUD is not the only addiction where semaglutide appears to have potential benefit. Cohort studies conducted by Volkow and her colleagues have suggested as much as a 78% reduced risk or opioid overdose in patients with comorbid obesity and type 2 diabetes) and a 44% reduction in cannabis use disorder in type 2 diabetes patients without a prior cannabis use disorder history.
Unclear Mechanisms, Multiple Theories
It’s not entirely clear how semaglutide provides a path for addicts to reduce their cravings or which patients might benefit most.
Preclinical studies have suggested that GLP-1 receptors are expressed throughout the mesolimbic dopamine system and transmit dopamine directly to reward centers in the forebrain, for example, the nucleus accumbens. The drugs appear to reduce dopamine release and transmission to these reward centers, as well as to areas that are responsible for impulse control.
“What we’re seeing is counteracting mechanisms that allow you to self-regulate are also involved in addiction, but I don’t know to what extent these medications could help strengthen that,” said Volkow.
Henry Kranzler, MD, professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, has a paper in press looking at genetic correlation between body mass index (BMI) and AUD. “Genetic analysis showed that many of the same genes are working in both disorders but in opposite directions,” he said.
The bottom line is that “they share genetics, but by no means are they the same; this gives us reason to believe that the GLP-1s could be beneficial in obesity but not nearly as beneficial for treating addiction,” said Kranzler.
Behind Closed Doors
Like many people with overweight or obesity who are on semaglutide, Bridget Pilloud, a writer who divides her time between Washington State and Arizona, no longer has any desire to drink.
“I used to really enjoy sitting and slowly sipping an Old Fashioned. I used to really enjoy specific whiskeys. Now, I don’t even like the flavor; the pleasure of drinking is gone,” she said.
Inexplicably, Pilloud said that she’s also given up compulsive shopping; “The hunt and acquisition of it was always really delicious to me,” she said.
Pilloud’s experience is not unique. Angela Fitch, MD, an obesity medicine specialist, co-founder and CMO of knownwell health, and former president of the Obesity Medicine Association, has had patients on semaglutide tell her that they’re not shopping as much.
But self-reports about alcohol consumption are far more common.
A 2023 analysis of social media posts reinforced that the experience is quite common, albeit self-reported.
Researchers used machine learning attribution mapping of 68,250 posts related to GLP-1 or GLP-1/glucose-dependent insulinotropic polypeptide agonists on the Reddit platform. Among the 1580 alcohol-related posts, 71% (1134/1580) of users of either drug said they had reduced cravings and decreased desire to drink. In a remote companion study of 153 people with obesity taking semaglutide (n = 56), tirzepatide (n = 50), or neither (n = 47), there appeared to be a reduced suppression of the desire to consume alcohol, with users reporting fewer drinks and binge episodes than control individuals.
Self-reports also underscored the association between either of the medications and less stimulating/sedative effects of alcohol compared with before starting the medications and to controls.
Behind closed doors, there appears to be as much chatter about the potential of these agents for AUD and other addiction disorders as there are questions about factors like treatment duration, safety of long-term, chronic use, and dosage.
“We don’t have data around people with normal weight and how much risk that is to them if they start taking these medications for addiction and reduce their BMI as low as 18,” said Fitch.
There’s also the question of when and how to wean patients off the medications, a consideration that is quite important for patients with addiction problems, said Volkow.
“What happens when you become addicted to drugs is that you start to degrade social support systems needed for well-being,” she explained. “The big difference with drugs versus foods is that you can live happily with no drugs at all, whereas you die if you don’t eat. So, there are greater challenges in the ability to change the environment (eg, help stabilize everyday life so people have alternative reinforcers) when you remove the reward.”
Additional considerations range from overuse and the development of treatment-resistant obesity to the need to ensure that patients on these drugs receive ongoing management and, of course, access, noted Fitch.
Still, the NIDA coffers are open. “We’re waiting for proposals,” said Volkow.
Fitch is cofounder and CMO of knownwell health. Volkow reported no relevant financial relationships. Kranzler is a member of advisory boards for Altimmune, Clearmind Medicine, Dicerna Pharmaceuticals, Enthion Pharmaceuticals, Eli Lilly and Company, and Sophrosyne Pharmaceuticals; a consultant to Sobrera Pharma and Altimmune; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the past 3 years by Alkermes, Dicerna Pharmaceuticals, Ethypharm, Imbrium, Indivior, Kinnov, Eli Lilly, Otsuka, and Pear; and a holder of US patent 10,900,082 titled: “Genotype-guided dosing of opioid agonists,” issued on January 26, 2021.
A version of this article appeared on Medscape.com.