Lung Cancer

Oncology fellows who completed diversity, equity, and inclusion (DEI) training report that they feel more confident about responding to different types of discrimination, both when directed at them personally and when directed at others.

The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.

“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”

Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.

The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).

At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.

First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.

Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.

Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.

“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”

Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.

The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.

The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.

Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.

Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.

“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”

No funding for the study was reported.

A version of this article first appeared on Medscape.com.

Oncology fellows who completed diversity, equity, and inclusion (DEI) training report that they feel more confident about responding to different types of discrimination, both when directed at them personally and when directed at others.

The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.

“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”

Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.

The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).

At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.

First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.

Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.

Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.

“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”

Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.

The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.

The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.

Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.

Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.

“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”

No funding for the study was reported.

A version of this article first appeared on Medscape.com.

Oncology fellows who completed diversity, equity, and inclusion (DEI) training report that they feel more confident about responding to different types of discrimination, both when directed at them personally and when directed at others.

The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.

“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”

Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.

The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).

At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.

First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.

Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.

Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.

“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”

Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.

The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.

The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.

Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.

Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.

“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”

No funding for the study was reported.

A version of this article first appeared on Medscape.com.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

CHICAGO – Having cancer is a known risk factor for thrombosis. A patient with cancer has a fourfold risk of developing venous thromboembolism (VTE).

This risk may be increased by certain cancer drugs, which seems to be the case for the combination of innovative targeted therapies lazertinib-amivantamab, as shown in patients with advanced or metastatic non–small cell lung cancer.

A study of this increased risk of VTE was presented by Nicolas Girard, MD, a respiratory medicine specialist at Curie-Montsouris Chest Center in Paris, during the annual meeting of the American Society of Clinical Oncology. Understanding and preventing this side effect of novel treatments could help patients for whom such medications are effective avoid the need to stop using them prematurely.
 

Combination therapies

Amivantamab is an EGFR and cMET bispecific antibody, and lazertinib is a third-generation EGFR tyrosine kinase inhibitor. Prescribed after osimertinib or after osimertinib plus chemotherapy, this combination of amivantamab and lazertinib has been evaluated in several cohorts of patients with EGFR-mutated advanced non–small cell lung cancer in whom targeted therapy and chemotherapy has failed.

The antitumor activity appears to be improved when both therapies are given in combination. The side effects generally are acceptable. It is these side effects, particularly the rate of VTEs, that Dr. Girard and his colleagues are interested in.

The researchers collated the data from the ongoing CHRYSALIS, CHRYSALIS-2, and LASER201 clinical trials, which assess the efficacy of these new agents as monotherapy or in combination. They initially investigated all reported thrombotic events and ruled out those that occurred during or after the 30 days before disease progression.
 

Increased thrombosis risk

The analysis included 560 patients who had been given amivantamab as monotherapy, 536 patients who had received amivantamab plus lazertinib in combination, and 252 who had taken lazertinib as monotherapy. The incidence of thromboembolic events was higher among patients who received amivantamab plus lazertinib in combination (21%) than in those who were given amivantamab (11%) or lazertinib (11%) as monotherapy.

The first thromboembolic event occurred an average of 84.5 days after starting treatment with amivantamab, 79 days after starting the combination therapy, and 170 days after starting treatment with lazertinib. For the amivantamab plus lazertinib combination, most VTEs developed in the first 4 months of treatment. The most common VTEs were pulmonary embolism and deep vein thrombosis.

The incidence of severe thrombotic events (grade ≥ 3), which was relatively low (amivantamab, 5%; amivantamab plus lazertinib, 6%; lazertinib, 6%) was similar regardless of the treatment, and there were no grade 5 thrombotic events among patients treated with the combination of both targeted therapies.

The significant risk factors for VTEs identified in this study were being age 60 years or older, having a score of 1 on the ECOG Performance Status Scale, and response to treatment (P < .05).

At a press conference organized by the Institut Curie before the ASCO conference, Dr. Girard said, “There has been shown to be an increased risk of blood clots with the use of this combination of targeted therapies. Preventive measures should therefore also be put forward, such as adding anticoagulant medication. This is an important study for the further development of these therapies.”

In a press release, the respiratory medicine specialist noted, “Institut Curie is particularly alert to the issue of the risk of thrombosis arising in cancer patients.” The DASTO project, dedicated to this issue and headed by the Institut Curie, “aims to cross-reference data sourced from several French cancer centers with data from the social security system to understand the risk factors, improve patient treatment, make changes to the care pathway, and prevent this unwanted occurrence from arising.”

Dr. Girard has direct links with Amgen, AstraZeneca, AbbVie, BMS, Daiichi Sankyo, Ipsen, Janssen, Roche, Lilly, Medtronic, MSD, Novartis, OSE Pharma, Pfizer, Sanofi, and Sivan.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

CHICAGO – Having cancer is a known risk factor for thrombosis. A patient with cancer has a fourfold risk of developing venous thromboembolism (VTE).

This risk may be increased by certain cancer drugs, which seems to be the case for the combination of innovative targeted therapies lazertinib-amivantamab, as shown in patients with advanced or metastatic non–small cell lung cancer.

A study of this increased risk of VTE was presented by Nicolas Girard, MD, a respiratory medicine specialist at Curie-Montsouris Chest Center in Paris, during the annual meeting of the American Society of Clinical Oncology. Understanding and preventing this side effect of novel treatments could help patients for whom such medications are effective avoid the need to stop using them prematurely.
 

Combination therapies

Amivantamab is an EGFR and cMET bispecific antibody, and lazertinib is a third-generation EGFR tyrosine kinase inhibitor. Prescribed after osimertinib or after osimertinib plus chemotherapy, this combination of amivantamab and lazertinib has been evaluated in several cohorts of patients with EGFR-mutated advanced non–small cell lung cancer in whom targeted therapy and chemotherapy has failed.

The antitumor activity appears to be improved when both therapies are given in combination. The side effects generally are acceptable. It is these side effects, particularly the rate of VTEs, that Dr. Girard and his colleagues are interested in.

The researchers collated the data from the ongoing CHRYSALIS, CHRYSALIS-2, and LASER201 clinical trials, which assess the efficacy of these new agents as monotherapy or in combination. They initially investigated all reported thrombotic events and ruled out those that occurred during or after the 30 days before disease progression.
 

Increased thrombosis risk

The analysis included 560 patients who had been given amivantamab as monotherapy, 536 patients who had received amivantamab plus lazertinib in combination, and 252 who had taken lazertinib as monotherapy. The incidence of thromboembolic events was higher among patients who received amivantamab plus lazertinib in combination (21%) than in those who were given amivantamab (11%) or lazertinib (11%) as monotherapy.

The first thromboembolic event occurred an average of 84.5 days after starting treatment with amivantamab, 79 days after starting the combination therapy, and 170 days after starting treatment with lazertinib. For the amivantamab plus lazertinib combination, most VTEs developed in the first 4 months of treatment. The most common VTEs were pulmonary embolism and deep vein thrombosis.

The incidence of severe thrombotic events (grade ≥ 3), which was relatively low (amivantamab, 5%; amivantamab plus lazertinib, 6%; lazertinib, 6%) was similar regardless of the treatment, and there were no grade 5 thrombotic events among patients treated with the combination of both targeted therapies.

The significant risk factors for VTEs identified in this study were being age 60 years or older, having a score of 1 on the ECOG Performance Status Scale, and response to treatment (P < .05).

At a press conference organized by the Institut Curie before the ASCO conference, Dr. Girard said, “There has been shown to be an increased risk of blood clots with the use of this combination of targeted therapies. Preventive measures should therefore also be put forward, such as adding anticoagulant medication. This is an important study for the further development of these therapies.”

In a press release, the respiratory medicine specialist noted, “Institut Curie is particularly alert to the issue of the risk of thrombosis arising in cancer patients.” The DASTO project, dedicated to this issue and headed by the Institut Curie, “aims to cross-reference data sourced from several French cancer centers with data from the social security system to understand the risk factors, improve patient treatment, make changes to the care pathway, and prevent this unwanted occurrence from arising.”

Dr. Girard has direct links with Amgen, AstraZeneca, AbbVie, BMS, Daiichi Sankyo, Ipsen, Janssen, Roche, Lilly, Medtronic, MSD, Novartis, OSE Pharma, Pfizer, Sanofi, and Sivan.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

CHICAGO – Having cancer is a known risk factor for thrombosis. A patient with cancer has a fourfold risk of developing venous thromboembolism (VTE).

This risk may be increased by certain cancer drugs, which seems to be the case for the combination of innovative targeted therapies lazertinib-amivantamab, as shown in patients with advanced or metastatic non–small cell lung cancer.

A study of this increased risk of VTE was presented by Nicolas Girard, MD, a respiratory medicine specialist at Curie-Montsouris Chest Center in Paris, during the annual meeting of the American Society of Clinical Oncology. Understanding and preventing this side effect of novel treatments could help patients for whom such medications are effective avoid the need to stop using them prematurely.
 

Combination therapies

Amivantamab is an EGFR and cMET bispecific antibody, and lazertinib is a third-generation EGFR tyrosine kinase inhibitor. Prescribed after osimertinib or after osimertinib plus chemotherapy, this combination of amivantamab and lazertinib has been evaluated in several cohorts of patients with EGFR-mutated advanced non–small cell lung cancer in whom targeted therapy and chemotherapy has failed.

The antitumor activity appears to be improved when both therapies are given in combination. The side effects generally are acceptable. It is these side effects, particularly the rate of VTEs, that Dr. Girard and his colleagues are interested in.

The researchers collated the data from the ongoing CHRYSALIS, CHRYSALIS-2, and LASER201 clinical trials, which assess the efficacy of these new agents as monotherapy or in combination. They initially investigated all reported thrombotic events and ruled out those that occurred during or after the 30 days before disease progression.
 

Increased thrombosis risk

The analysis included 560 patients who had been given amivantamab as monotherapy, 536 patients who had received amivantamab plus lazertinib in combination, and 252 who had taken lazertinib as monotherapy. The incidence of thromboembolic events was higher among patients who received amivantamab plus lazertinib in combination (21%) than in those who were given amivantamab (11%) or lazertinib (11%) as monotherapy.

The first thromboembolic event occurred an average of 84.5 days after starting treatment with amivantamab, 79 days after starting the combination therapy, and 170 days after starting treatment with lazertinib. For the amivantamab plus lazertinib combination, most VTEs developed in the first 4 months of treatment. The most common VTEs were pulmonary embolism and deep vein thrombosis.

The incidence of severe thrombotic events (grade ≥ 3), which was relatively low (amivantamab, 5%; amivantamab plus lazertinib, 6%; lazertinib, 6%) was similar regardless of the treatment, and there were no grade 5 thrombotic events among patients treated with the combination of both targeted therapies.

The significant risk factors for VTEs identified in this study were being age 60 years or older, having a score of 1 on the ECOG Performance Status Scale, and response to treatment (P < .05).

At a press conference organized by the Institut Curie before the ASCO conference, Dr. Girard said, “There has been shown to be an increased risk of blood clots with the use of this combination of targeted therapies. Preventive measures should therefore also be put forward, such as adding anticoagulant medication. This is an important study for the further development of these therapies.”

In a press release, the respiratory medicine specialist noted, “Institut Curie is particularly alert to the issue of the risk of thrombosis arising in cancer patients.” The DASTO project, dedicated to this issue and headed by the Institut Curie, “aims to cross-reference data sourced from several French cancer centers with data from the social security system to understand the risk factors, improve patient treatment, make changes to the care pathway, and prevent this unwanted occurrence from arising.”

Dr. Girard has direct links with Amgen, AstraZeneca, AbbVie, BMS, Daiichi Sankyo, Ipsen, Janssen, Roche, Lilly, Medtronic, MSD, Novartis, OSE Pharma, Pfizer, Sanofi, and Sivan.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

Only 12.8% of eligible adults get CT screening for lung cancer, despite recommendations from the U.S. Preventive Services Task Force.

Kristin G. Maki, PhD, with Karmanos Cancer Institute, Wayne State University, Detroit, led a team that estimated lung cancer screening (LCS) from the 2021 Behavioral Risk Factor Surveillance System in four states (Maine, Michigan, New Jersey, and Rhode Island).

“Increasing LCS among eligible adults is a national priority,” the authors wrote in the study, published online in JAMA Network Open. Lung cancer remains the top cause of cancer in the United States and smoking accounts for approximately 90% of cases.
 

Screening much higher for other cancers

The authors pointed out that screening rates for eligible people are much higher for other cancers. Melzer and colleagues wrote in a 2021 editorial that breast and colon cancer screening rates are near 70% “despite combined annual death rates less than two-thirds that of lung cancer.”

The USPSTF updated its recommendations for lung cancer screening in March 2021.

Eligibility now includes anyone aged between 50 and 80 years who has smoked at least 20 pack-years and either still smokes or quit within the last 15 years.

The researchers found that, when comparing screening by health status, the highest odds for screening were seen in those who reported they were in poor health, which is concerning, the authors note, because those patients may not be healthy enough to benefit from treatment for their lung cancer.

The odds ratio for getting screening was 2.88 (95% confidence interval, 0.85-9.77) times higher than that of the reference group, which reported excellent health.
 

Rates differ by state

Consistent with previous studies, this analysis found that screening rates differed by state. Their analysis, for example, showed a higher likelihood of screening for respondents in Rhode Island, compared with Maine (OR, 1.96; 95% CI, 1.05-3.67; P = .03).

Patients who reported having a primary health professional were more than five times more likely to undergo screening, compared with those without one (OR, 5.62; 95% CI, 1.19-26.49).

The authors said their results also highlight the need for Medicare coverage for screening as those with public insurance had lower odds of screening than those with private insurance (OR, 0.81; 95% CI, 0.42-1.56).

Neelima Navuluri, MD, assistant professor in the division of pulmonary, allergy, and critical care at Duke University and the Duke Global Health Institute, both in Durham, N.C., pointed out that the study highlights age, smoking status, and health care access as key factors associated with lack of uptake.
 

Work needed on all levels

Dr. Navuluri said in an interview that multifaceted patient-, provider- and system-level interventions are needed to improve screening rates.

“For example, we need more community engagement to increase knowledge and awareness of eligibility for lung cancer screening,” she said.

She highlighted the need for interventions around improving and streamlining shared decision-making conversations about screening (a CMS requirement that does not exist for other cancer screening).

Emphasis is needed on younger age groups, people who currently smoke, and communities of color as well as policy to improve insurance coverage of screening, she said.

Dr. Navuluri, who also works with the Durham Veterans Affairs Medical Center, was lead author on a study published in JAMA Network Open on racial disparities in screening among veterans.

“We demonstrate similar findings related to age, smoking status, and poor health status,” she said. “We discuss the need for more qualitative studies to better understand the role of these factors as well as implementation studies to assess effectiveness of various interventions to improve disparities in lung cancer screening rates.”

“Research to identify facilitators for LCS among persons who currently smoke is needed, including a focus on the role of stigma as a barrier to screening,” they wrote.

One coauthor is supported by the cancer prevention and research training program at the University of Texas MD Anderson Cancer Center and the Cancer Prevention and Research Institute of Texas. No other disclosures were reported. Dr. Navuluri receives funding from the National Comprehensive Cancer Network for work on lung cancer screening.

Only 12.8% of eligible adults get CT screening for lung cancer, despite recommendations from the U.S. Preventive Services Task Force.

Kristin G. Maki, PhD, with Karmanos Cancer Institute, Wayne State University, Detroit, led a team that estimated lung cancer screening (LCS) from the 2021 Behavioral Risk Factor Surveillance System in four states (Maine, Michigan, New Jersey, and Rhode Island).

“Increasing LCS among eligible adults is a national priority,” the authors wrote in the study, published online in JAMA Network Open. Lung cancer remains the top cause of cancer in the United States and smoking accounts for approximately 90% of cases.
 

Screening much higher for other cancers

The authors pointed out that screening rates for eligible people are much higher for other cancers. Melzer and colleagues wrote in a 2021 editorial that breast and colon cancer screening rates are near 70% “despite combined annual death rates less than two-thirds that of lung cancer.”

The USPSTF updated its recommendations for lung cancer screening in March 2021.

Eligibility now includes anyone aged between 50 and 80 years who has smoked at least 20 pack-years and either still smokes or quit within the last 15 years.

The researchers found that, when comparing screening by health status, the highest odds for screening were seen in those who reported they were in poor health, which is concerning, the authors note, because those patients may not be healthy enough to benefit from treatment for their lung cancer.

The odds ratio for getting screening was 2.88 (95% confidence interval, 0.85-9.77) times higher than that of the reference group, which reported excellent health.
 

Rates differ by state

Consistent with previous studies, this analysis found that screening rates differed by state. Their analysis, for example, showed a higher likelihood of screening for respondents in Rhode Island, compared with Maine (OR, 1.96; 95% CI, 1.05-3.67; P = .03).

Patients who reported having a primary health professional were more than five times more likely to undergo screening, compared with those without one (OR, 5.62; 95% CI, 1.19-26.49).

The authors said their results also highlight the need for Medicare coverage for screening as those with public insurance had lower odds of screening than those with private insurance (OR, 0.81; 95% CI, 0.42-1.56).

Neelima Navuluri, MD, assistant professor in the division of pulmonary, allergy, and critical care at Duke University and the Duke Global Health Institute, both in Durham, N.C., pointed out that the study highlights age, smoking status, and health care access as key factors associated with lack of uptake.
 

Work needed on all levels

Dr. Navuluri said in an interview that multifaceted patient-, provider- and system-level interventions are needed to improve screening rates.

“For example, we need more community engagement to increase knowledge and awareness of eligibility for lung cancer screening,” she said.

She highlighted the need for interventions around improving and streamlining shared decision-making conversations about screening (a CMS requirement that does not exist for other cancer screening).

Emphasis is needed on younger age groups, people who currently smoke, and communities of color as well as policy to improve insurance coverage of screening, she said.

Dr. Navuluri, who also works with the Durham Veterans Affairs Medical Center, was lead author on a study published in JAMA Network Open on racial disparities in screening among veterans.

“We demonstrate similar findings related to age, smoking status, and poor health status,” she said. “We discuss the need for more qualitative studies to better understand the role of these factors as well as implementation studies to assess effectiveness of various interventions to improve disparities in lung cancer screening rates.”

“Research to identify facilitators for LCS among persons who currently smoke is needed, including a focus on the role of stigma as a barrier to screening,” they wrote.

One coauthor is supported by the cancer prevention and research training program at the University of Texas MD Anderson Cancer Center and the Cancer Prevention and Research Institute of Texas. No other disclosures were reported. Dr. Navuluri receives funding from the National Comprehensive Cancer Network for work on lung cancer screening.

Only 12.8% of eligible adults get CT screening for lung cancer, despite recommendations from the U.S. Preventive Services Task Force.

Kristin G. Maki, PhD, with Karmanos Cancer Institute, Wayne State University, Detroit, led a team that estimated lung cancer screening (LCS) from the 2021 Behavioral Risk Factor Surveillance System in four states (Maine, Michigan, New Jersey, and Rhode Island).

“Increasing LCS among eligible adults is a national priority,” the authors wrote in the study, published online in JAMA Network Open. Lung cancer remains the top cause of cancer in the United States and smoking accounts for approximately 90% of cases.
 

Screening much higher for other cancers

The authors pointed out that screening rates for eligible people are much higher for other cancers. Melzer and colleagues wrote in a 2021 editorial that breast and colon cancer screening rates are near 70% “despite combined annual death rates less than two-thirds that of lung cancer.”

The USPSTF updated its recommendations for lung cancer screening in March 2021.

Eligibility now includes anyone aged between 50 and 80 years who has smoked at least 20 pack-years and either still smokes or quit within the last 15 years.

The researchers found that, when comparing screening by health status, the highest odds for screening were seen in those who reported they were in poor health, which is concerning, the authors note, because those patients may not be healthy enough to benefit from treatment for their lung cancer.

The odds ratio for getting screening was 2.88 (95% confidence interval, 0.85-9.77) times higher than that of the reference group, which reported excellent health.
 

Rates differ by state

Consistent with previous studies, this analysis found that screening rates differed by state. Their analysis, for example, showed a higher likelihood of screening for respondents in Rhode Island, compared with Maine (OR, 1.96; 95% CI, 1.05-3.67; P = .03).

Patients who reported having a primary health professional were more than five times more likely to undergo screening, compared with those without one (OR, 5.62; 95% CI, 1.19-26.49).

The authors said their results also highlight the need for Medicare coverage for screening as those with public insurance had lower odds of screening than those with private insurance (OR, 0.81; 95% CI, 0.42-1.56).

Neelima Navuluri, MD, assistant professor in the division of pulmonary, allergy, and critical care at Duke University and the Duke Global Health Institute, both in Durham, N.C., pointed out that the study highlights age, smoking status, and health care access as key factors associated with lack of uptake.
 

Work needed on all levels

Dr. Navuluri said in an interview that multifaceted patient-, provider- and system-level interventions are needed to improve screening rates.

“For example, we need more community engagement to increase knowledge and awareness of eligibility for lung cancer screening,” she said.

She highlighted the need for interventions around improving and streamlining shared decision-making conversations about screening (a CMS requirement that does not exist for other cancer screening).

Emphasis is needed on younger age groups, people who currently smoke, and communities of color as well as policy to improve insurance coverage of screening, she said.

Dr. Navuluri, who also works with the Durham Veterans Affairs Medical Center, was lead author on a study published in JAMA Network Open on racial disparities in screening among veterans.

“We demonstrate similar findings related to age, smoking status, and poor health status,” she said. “We discuss the need for more qualitative studies to better understand the role of these factors as well as implementation studies to assess effectiveness of various interventions to improve disparities in lung cancer screening rates.”

“Research to identify facilitators for LCS among persons who currently smoke is needed, including a focus on the role of stigma as a barrier to screening,” they wrote.

One coauthor is supported by the cancer prevention and research training program at the University of Texas MD Anderson Cancer Center and the Cancer Prevention and Research Institute of Texas. No other disclosures were reported. Dr. Navuluri receives funding from the National Comprehensive Cancer Network for work on lung cancer screening.

An electronic exhaled breath analyzer showed differences in breath profiles of patients with chronic obstructive pulmonary disease who did and did not develop lung cancer, based on data from a prospective study of approximately 800 individuals.

Lung cancer remains a major cause of death in patients with chronic obstructive pulmonary disease (COPD), but many cases may go undetected in the early stage because of lack of screening and lack of validated predictive biomarkers, wrote Rianne de Vries, PhD, of the University of Amsterdam, and colleagues.

Accurate, noninvasive tests to screen patients with COPD for lung cancer are needed, and molecular profiling of exhaled breath using electronic nose (eNose) technology has shown potential as a method of early detection by identifying patterns of exhaled volatile organic compounds (VOCs), they said.

In a study published in the journal Chest, the researchers reviewed data from 682 adults with COPD and 211 with lung cancer who were enrolled in BreathCloud, a multicenter, observational study of healthy controls and individuals with suspected or confirmed diagnosis of asthma, COPD, or lung cancer.

Patients’ breath profiles were collected at study enrollment, between May 2017 and November 2018, using a metal oxide semiconductor eNose (SpiroNose).

Data from the eNose included the highest sensor peak normalized to the most stable sensor and the ratio between sensor peak and breath hold point. These variables were combined into four principal components (PCs) that captured 78.4% of variance in the dataset, and training and validation sets were constructed for all subjects. The researchers calculated a receiver operating characteristic (ROC) curve, including the area under the curve (AUC).

All patients were treated with standard clinical care and were monitored for development of clinically diagnosed lung cancer for 2 years, confirmed via CT imaging. The mean age of the patients was 64 years, and demographics at baseline were similar for patients with and without lung cancer.

After exclusion of 116 patients with both COPD and lung cancer, the analysis showed an accuracy of 90% and a ROC-AUC of 0.95.

Within 2 years of study enrollment, 37 patients with COPD (5.4%) developed lung cancer. In training sets and validation sets, the principal components one, two, and three were significantly different in patients with COPD who developed lung cancer and those who did not, (P = .002, P < .001, P < .001, respectively). The ROC-AUCs of the testing and validation sets were 0.89 and 0.86, respectively.

“Interestingly, the VOC pattern associated with early development of lung cancer in COPD did not match to the pattern related to lung cancer stages, as the former was mainly captured by PC2 and the latter by PC3,” the researchers wrote in their discussion. “This suggests that early identification of upcoming clinically manifest lung cancer in patients with COPD by eNose is not driven by VOCs that are predominantly associated with a particular stage of the disease,” they said.

The findings were limited by several factors including the lack of CT scanning at baseline because of the real-world design, so the presence of any baseline tumors was unknown, although none of the COPD patients showed symptoms indicative of lung cancer at baseline, the researchers noted.

However, the results suggest that eNose technology can identify lung cancer-specific VOC patterns early in cancer development in COPD patients, which provides a possible opportunity for early intervention, they concluded.

The study received no outside funding. De Vries disclosed personal fees and a substantial interest in the start-up company Breathomix.

A version of this article first appeared on Medscape.com.

An electronic exhaled breath analyzer showed differences in breath profiles of patients with chronic obstructive pulmonary disease who did and did not develop lung cancer, based on data from a prospective study of approximately 800 individuals.

Lung cancer remains a major cause of death in patients with chronic obstructive pulmonary disease (COPD), but many cases may go undetected in the early stage because of lack of screening and lack of validated predictive biomarkers, wrote Rianne de Vries, PhD, of the University of Amsterdam, and colleagues.

Accurate, noninvasive tests to screen patients with COPD for lung cancer are needed, and molecular profiling of exhaled breath using electronic nose (eNose) technology has shown potential as a method of early detection by identifying patterns of exhaled volatile organic compounds (VOCs), they said.

In a study published in the journal Chest, the researchers reviewed data from 682 adults with COPD and 211 with lung cancer who were enrolled in BreathCloud, a multicenter, observational study of healthy controls and individuals with suspected or confirmed diagnosis of asthma, COPD, or lung cancer.

Patients’ breath profiles were collected at study enrollment, between May 2017 and November 2018, using a metal oxide semiconductor eNose (SpiroNose).

Data from the eNose included the highest sensor peak normalized to the most stable sensor and the ratio between sensor peak and breath hold point. These variables were combined into four principal components (PCs) that captured 78.4% of variance in the dataset, and training and validation sets were constructed for all subjects. The researchers calculated a receiver operating characteristic (ROC) curve, including the area under the curve (AUC).

All patients were treated with standard clinical care and were monitored for development of clinically diagnosed lung cancer for 2 years, confirmed via CT imaging. The mean age of the patients was 64 years, and demographics at baseline were similar for patients with and without lung cancer.

After exclusion of 116 patients with both COPD and lung cancer, the analysis showed an accuracy of 90% and a ROC-AUC of 0.95.

Within 2 years of study enrollment, 37 patients with COPD (5.4%) developed lung cancer. In training sets and validation sets, the principal components one, two, and three were significantly different in patients with COPD who developed lung cancer and those who did not, (P = .002, P < .001, P < .001, respectively). The ROC-AUCs of the testing and validation sets were 0.89 and 0.86, respectively.

“Interestingly, the VOC pattern associated with early development of lung cancer in COPD did not match to the pattern related to lung cancer stages, as the former was mainly captured by PC2 and the latter by PC3,” the researchers wrote in their discussion. “This suggests that early identification of upcoming clinically manifest lung cancer in patients with COPD by eNose is not driven by VOCs that are predominantly associated with a particular stage of the disease,” they said.

The findings were limited by several factors including the lack of CT scanning at baseline because of the real-world design, so the presence of any baseline tumors was unknown, although none of the COPD patients showed symptoms indicative of lung cancer at baseline, the researchers noted.

However, the results suggest that eNose technology can identify lung cancer-specific VOC patterns early in cancer development in COPD patients, which provides a possible opportunity for early intervention, they concluded.

The study received no outside funding. De Vries disclosed personal fees and a substantial interest in the start-up company Breathomix.

A version of this article first appeared on Medscape.com.

An electronic exhaled breath analyzer showed differences in breath profiles of patients with chronic obstructive pulmonary disease who did and did not develop lung cancer, based on data from a prospective study of approximately 800 individuals.

Lung cancer remains a major cause of death in patients with chronic obstructive pulmonary disease (COPD), but many cases may go undetected in the early stage because of lack of screening and lack of validated predictive biomarkers, wrote Rianne de Vries, PhD, of the University of Amsterdam, and colleagues.

Accurate, noninvasive tests to screen patients with COPD for lung cancer are needed, and molecular profiling of exhaled breath using electronic nose (eNose) technology has shown potential as a method of early detection by identifying patterns of exhaled volatile organic compounds (VOCs), they said.

In a study published in the journal Chest, the researchers reviewed data from 682 adults with COPD and 211 with lung cancer who were enrolled in BreathCloud, a multicenter, observational study of healthy controls and individuals with suspected or confirmed diagnosis of asthma, COPD, or lung cancer.

Patients’ breath profiles were collected at study enrollment, between May 2017 and November 2018, using a metal oxide semiconductor eNose (SpiroNose).

Data from the eNose included the highest sensor peak normalized to the most stable sensor and the ratio between sensor peak and breath hold point. These variables were combined into four principal components (PCs) that captured 78.4% of variance in the dataset, and training and validation sets were constructed for all subjects. The researchers calculated a receiver operating characteristic (ROC) curve, including the area under the curve (AUC).

All patients were treated with standard clinical care and were monitored for development of clinically diagnosed lung cancer for 2 years, confirmed via CT imaging. The mean age of the patients was 64 years, and demographics at baseline were similar for patients with and without lung cancer.

After exclusion of 116 patients with both COPD and lung cancer, the analysis showed an accuracy of 90% and a ROC-AUC of 0.95.

Within 2 years of study enrollment, 37 patients with COPD (5.4%) developed lung cancer. In training sets and validation sets, the principal components one, two, and three were significantly different in patients with COPD who developed lung cancer and those who did not, (P = .002, P < .001, P < .001, respectively). The ROC-AUCs of the testing and validation sets were 0.89 and 0.86, respectively.

“Interestingly, the VOC pattern associated with early development of lung cancer in COPD did not match to the pattern related to lung cancer stages, as the former was mainly captured by PC2 and the latter by PC3,” the researchers wrote in their discussion. “This suggests that early identification of upcoming clinically manifest lung cancer in patients with COPD by eNose is not driven by VOCs that are predominantly associated with a particular stage of the disease,” they said.

The findings were limited by several factors including the lack of CT scanning at baseline because of the real-world design, so the presence of any baseline tumors was unknown, although none of the COPD patients showed symptoms indicative of lung cancer at baseline, the researchers noted.

However, the results suggest that eNose technology can identify lung cancer-specific VOC patterns early in cancer development in COPD patients, which provides a possible opportunity for early intervention, they concluded.

The study received no outside funding. De Vries disclosed personal fees and a substantial interest in the start-up company Breathomix.

A version of this article first appeared on Medscape.com.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

A version of this article first appeared on Medscape.com.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

A version of this article first appeared on Medscape.com.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

A version of this article first appeared on Medscape.com.

Barry Bonds and Roger Clemens are two world-class baseball players who played well enough to earn enduring respect and admiration. However, their reputations have been permanently tainted by their use of performance-enhancing drugs. Although they are both undeniably gifted, we’ll never know where their natural talent ended and their unfair advantage began.

The medical oncology version of this scenario played out in front of our eyes at the ASCO 2023 Plenary Session featuring the ADAURA trial. In this case, the unfair advantage was clear: Nearly two-thirds of patients in the control arm did not cross over to a standard-of-care treatment at relapse.

The ADAURA trial tested the value of the third-generation oral EGFR inhibitor osimertinib vs. placebo for up to 3 years in patients with a resected stage IB-IIIA non–small cell lung cancer (NSCLC) harboring an activating EGFR mutation. Initially presented in the ASCO 2020 Plenary Session, the preliminary analysis for ADAURA demonstrated a remarkably favorable improvement in disease-free survival (DFS) in the osimertinib arm, which led to its prompt Food and Drug Administration approval in this setting.

At the time, I was among the more vocal critics of the fanfare around this trial. The DFS improvement was impressive but, in this context, represented a low threshold for FDA approval. We already knew that prior trials of other, less effective adjuvant EGFR inhibitors routinely improved DFS but ultimately failed to improve overall survival.

Although in some cases, a DFS benefit can be sufficient to warrant changing practice, I would argue that overall survival is the most critical endpoint in a curative setting by a wide margin. I would also argue that cost should be a consideration for a drug priced at $440,000 over 3 years in the United States. At the very least, we – patients, oncologists, payers – should want to clarify what we get for $440,000 per patient, especially if that money could be better spent on other things.

Of note, we need to know whether the same overall survival may be achieved in this setting by treating only patients whose disease relapses, avoiding both the cost and toxicity of continuous treatment.

The relevance of this question became even more acute when an updated version of the ADAURA trial showed that the DFS benefit from osimertinib began to erode immediately after patients completed active treatment. Although the DFS benefit remained excellent, the findings suggested that ADAURA may echo other adjuvant EGFR inhibitor trials: It may start out from a higher peak, but over time, the benefit of the drug may drop to the disappointing levels seen in other, similar drugs.

The overall survival data – the critical test in my mind – were presented at the ASCO Plenary Session. The results were highly positive, with a hazard ratio for overall survival of 0.49 and a similar benefit observed across all eligible disease stages.

As with the presentation of the DFS data in 2020, these results were accompanied by adulation during the session and fawning in the media. However, a subset of people in the audience, and on Twitter, voiced a major concern: In the control arm, only 38.5% of the patients whose disease had relapsed (79 of 205) ever received osimertinib.

Post-protocol treatment included reassurances that patients in the control arm were offered crossover to osimertinib, but this only occurred starting in April 2020 and only when the treating investigator requested it.

The fact that only a minority of patients in the control arm ever received osimertinib means that ADAURA is not a trial that tests adjuvant osimertinib to osimertinib at relapse, the prevailing standard of care in the United States and the preferred treatment in this setting, based on NCCN guidelines for patients with relapsed/metastatic EGFR mutation–positive NSCLC since the FDA approval in April 2018.

The change in standard of care in the United States and some other countries did not lead to an amendment in the trial, based on the argument that the trial was designed with DFS as the primary endpoint and that patients in the control arm are effectively off trial at relapse. That means patients would receive their country’s standard of care, which may be below, or different from, the standard in the United States or other parts of the world.

While defensible, others considered the low rate of osimertinib delivery in the control arm a serious flaw in the trial design and arguably an ethical problem.

Given this trial design, it’s important to question whether the trial magnified the difference in overall survival between the two arms compared with the standard of care in countries where adjuvant osimertinib will ultimately be marketed. Although I strongly suspect that the overall survival difference would have been significant without the disparity in access to osimertinib in the control arm, we will never know the magnitude of that difference.

With the current design, the trial demonstrates that osimertinib is associated with improved survival in 100% of patients with EGFR mutation–positive NSCLC who receive the agent vs. 38.5% of patients receiving it at some point after relapse.

At the end of the day, ADAURA followed conventional trial rules, which led to a windfall of accolades at the cost of suboptimal care for many of the patients randomly assigned to the control arm.

We need to decide as an oncology community whether we want to accept a system that confers rewards for stakeholders at the expense of patients enrolled in the trial.

We have developed a system that not only permits but depends on global trials enrolling many patients from countries with staging and off-protocol oncology care below standards of care in other parts of the world – effectively condoning and perpetuating disparities in optimal care globally. I am also saddened that some of the most respected leaders in our field have become upset when I question the ethics of accepting this system, one that I believe we have agency to change.

The question here is not whether osimertinib is a good drug; it is remarkably effective for patients with EGFR mutation–positive NSCLC. The question is how to design trials in a fair and balanced way that doesn’t compromise patient care or ethical standards.

If people think my assessment is too harsh, I openly welcome debate.

Bottom line: The ADAURA trial lays bare deeper problems with clinical trial design, and I would challenge readers to reflect on our clinical trial culture in oncology, which offers a system of rules that rewards denying the best identified care for patients on our clinical trials.

At the very least, should we celebrate these wins without fully acknowledging these problems?
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

A version of this article first appeared on Medscape.com.

Barry Bonds and Roger Clemens are two world-class baseball players who played well enough to earn enduring respect and admiration. However, their reputations have been permanently tainted by their use of performance-enhancing drugs. Although they are both undeniably gifted, we’ll never know where their natural talent ended and their unfair advantage began.

The medical oncology version of this scenario played out in front of our eyes at the ASCO 2023 Plenary Session featuring the ADAURA trial. In this case, the unfair advantage was clear: Nearly two-thirds of patients in the control arm did not cross over to a standard-of-care treatment at relapse.

The ADAURA trial tested the value of the third-generation oral EGFR inhibitor osimertinib vs. placebo for up to 3 years in patients with a resected stage IB-IIIA non–small cell lung cancer (NSCLC) harboring an activating EGFR mutation. Initially presented in the ASCO 2020 Plenary Session, the preliminary analysis for ADAURA demonstrated a remarkably favorable improvement in disease-free survival (DFS) in the osimertinib arm, which led to its prompt Food and Drug Administration approval in this setting.

At the time, I was among the more vocal critics of the fanfare around this trial. The DFS improvement was impressive but, in this context, represented a low threshold for FDA approval. We already knew that prior trials of other, less effective adjuvant EGFR inhibitors routinely improved DFS but ultimately failed to improve overall survival.

Although in some cases, a DFS benefit can be sufficient to warrant changing practice, I would argue that overall survival is the most critical endpoint in a curative setting by a wide margin. I would also argue that cost should be a consideration for a drug priced at $440,000 over 3 years in the United States. At the very least, we – patients, oncologists, payers – should want to clarify what we get for $440,000 per patient, especially if that money could be better spent on other things.

Of note, we need to know whether the same overall survival may be achieved in this setting by treating only patients whose disease relapses, avoiding both the cost and toxicity of continuous treatment.

The relevance of this question became even more acute when an updated version of the ADAURA trial showed that the DFS benefit from osimertinib began to erode immediately after patients completed active treatment. Although the DFS benefit remained excellent, the findings suggested that ADAURA may echo other adjuvant EGFR inhibitor trials: It may start out from a higher peak, but over time, the benefit of the drug may drop to the disappointing levels seen in other, similar drugs.

The overall survival data – the critical test in my mind – were presented at the ASCO Plenary Session. The results were highly positive, with a hazard ratio for overall survival of 0.49 and a similar benefit observed across all eligible disease stages.

As with the presentation of the DFS data in 2020, these results were accompanied by adulation during the session and fawning in the media. However, a subset of people in the audience, and on Twitter, voiced a major concern: In the control arm, only 38.5% of the patients whose disease had relapsed (79 of 205) ever received osimertinib.

Post-protocol treatment included reassurances that patients in the control arm were offered crossover to osimertinib, but this only occurred starting in April 2020 and only when the treating investigator requested it.

The fact that only a minority of patients in the control arm ever received osimertinib means that ADAURA is not a trial that tests adjuvant osimertinib to osimertinib at relapse, the prevailing standard of care in the United States and the preferred treatment in this setting, based on NCCN guidelines for patients with relapsed/metastatic EGFR mutation–positive NSCLC since the FDA approval in April 2018.

The change in standard of care in the United States and some other countries did not lead to an amendment in the trial, based on the argument that the trial was designed with DFS as the primary endpoint and that patients in the control arm are effectively off trial at relapse. That means patients would receive their country’s standard of care, which may be below, or different from, the standard in the United States or other parts of the world.

While defensible, others considered the low rate of osimertinib delivery in the control arm a serious flaw in the trial design and arguably an ethical problem.

Given this trial design, it’s important to question whether the trial magnified the difference in overall survival between the two arms compared with the standard of care in countries where adjuvant osimertinib will ultimately be marketed. Although I strongly suspect that the overall survival difference would have been significant without the disparity in access to osimertinib in the control arm, we will never know the magnitude of that difference.

With the current design, the trial demonstrates that osimertinib is associated with improved survival in 100% of patients with EGFR mutation–positive NSCLC who receive the agent vs. 38.5% of patients receiving it at some point after relapse.

At the end of the day, ADAURA followed conventional trial rules, which led to a windfall of accolades at the cost of suboptimal care for many of the patients randomly assigned to the control arm.

We need to decide as an oncology community whether we want to accept a system that confers rewards for stakeholders at the expense of patients enrolled in the trial.

We have developed a system that not only permits but depends on global trials enrolling many patients from countries with staging and off-protocol oncology care below standards of care in other parts of the world – effectively condoning and perpetuating disparities in optimal care globally. I am also saddened that some of the most respected leaders in our field have become upset when I question the ethics of accepting this system, one that I believe we have agency to change.

The question here is not whether osimertinib is a good drug; it is remarkably effective for patients with EGFR mutation–positive NSCLC. The question is how to design trials in a fair and balanced way that doesn’t compromise patient care or ethical standards.

If people think my assessment is too harsh, I openly welcome debate.

Bottom line: The ADAURA trial lays bare deeper problems with clinical trial design, and I would challenge readers to reflect on our clinical trial culture in oncology, which offers a system of rules that rewards denying the best identified care for patients on our clinical trials.

At the very least, should we celebrate these wins without fully acknowledging these problems?
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

A version of this article first appeared on Medscape.com.

Barry Bonds and Roger Clemens are two world-class baseball players who played well enough to earn enduring respect and admiration. However, their reputations have been permanently tainted by their use of performance-enhancing drugs. Although they are both undeniably gifted, we’ll never know where their natural talent ended and their unfair advantage began.

The medical oncology version of this scenario played out in front of our eyes at the ASCO 2023 Plenary Session featuring the ADAURA trial. In this case, the unfair advantage was clear: Nearly two-thirds of patients in the control arm did not cross over to a standard-of-care treatment at relapse.

The ADAURA trial tested the value of the third-generation oral EGFR inhibitor osimertinib vs. placebo for up to 3 years in patients with a resected stage IB-IIIA non–small cell lung cancer (NSCLC) harboring an activating EGFR mutation. Initially presented in the ASCO 2020 Plenary Session, the preliminary analysis for ADAURA demonstrated a remarkably favorable improvement in disease-free survival (DFS) in the osimertinib arm, which led to its prompt Food and Drug Administration approval in this setting.

At the time, I was among the more vocal critics of the fanfare around this trial. The DFS improvement was impressive but, in this context, represented a low threshold for FDA approval. We already knew that prior trials of other, less effective adjuvant EGFR inhibitors routinely improved DFS but ultimately failed to improve overall survival.

Although in some cases, a DFS benefit can be sufficient to warrant changing practice, I would argue that overall survival is the most critical endpoint in a curative setting by a wide margin. I would also argue that cost should be a consideration for a drug priced at $440,000 over 3 years in the United States. At the very least, we – patients, oncologists, payers – should want to clarify what we get for $440,000 per patient, especially if that money could be better spent on other things.

Of note, we need to know whether the same overall survival may be achieved in this setting by treating only patients whose disease relapses, avoiding both the cost and toxicity of continuous treatment.

The relevance of this question became even more acute when an updated version of the ADAURA trial showed that the DFS benefit from osimertinib began to erode immediately after patients completed active treatment. Although the DFS benefit remained excellent, the findings suggested that ADAURA may echo other adjuvant EGFR inhibitor trials: It may start out from a higher peak, but over time, the benefit of the drug may drop to the disappointing levels seen in other, similar drugs.

The overall survival data – the critical test in my mind – were presented at the ASCO Plenary Session. The results were highly positive, with a hazard ratio for overall survival of 0.49 and a similar benefit observed across all eligible disease stages.

As with the presentation of the DFS data in 2020, these results were accompanied by adulation during the session and fawning in the media. However, a subset of people in the audience, and on Twitter, voiced a major concern: In the control arm, only 38.5% of the patients whose disease had relapsed (79 of 205) ever received osimertinib.

Post-protocol treatment included reassurances that patients in the control arm were offered crossover to osimertinib, but this only occurred starting in April 2020 and only when the treating investigator requested it.

The fact that only a minority of patients in the control arm ever received osimertinib means that ADAURA is not a trial that tests adjuvant osimertinib to osimertinib at relapse, the prevailing standard of care in the United States and the preferred treatment in this setting, based on NCCN guidelines for patients with relapsed/metastatic EGFR mutation–positive NSCLC since the FDA approval in April 2018.

The change in standard of care in the United States and some other countries did not lead to an amendment in the trial, based on the argument that the trial was designed with DFS as the primary endpoint and that patients in the control arm are effectively off trial at relapse. That means patients would receive their country’s standard of care, which may be below, or different from, the standard in the United States or other parts of the world.

While defensible, others considered the low rate of osimertinib delivery in the control arm a serious flaw in the trial design and arguably an ethical problem.

Given this trial design, it’s important to question whether the trial magnified the difference in overall survival between the two arms compared with the standard of care in countries where adjuvant osimertinib will ultimately be marketed. Although I strongly suspect that the overall survival difference would have been significant without the disparity in access to osimertinib in the control arm, we will never know the magnitude of that difference.

With the current design, the trial demonstrates that osimertinib is associated with improved survival in 100% of patients with EGFR mutation–positive NSCLC who receive the agent vs. 38.5% of patients receiving it at some point after relapse.

At the end of the day, ADAURA followed conventional trial rules, which led to a windfall of accolades at the cost of suboptimal care for many of the patients randomly assigned to the control arm.

We need to decide as an oncology community whether we want to accept a system that confers rewards for stakeholders at the expense of patients enrolled in the trial.

We have developed a system that not only permits but depends on global trials enrolling many patients from countries with staging and off-protocol oncology care below standards of care in other parts of the world – effectively condoning and perpetuating disparities in optimal care globally. I am also saddened that some of the most respected leaders in our field have become upset when I question the ethics of accepting this system, one that I believe we have agency to change.

The question here is not whether osimertinib is a good drug; it is remarkably effective for patients with EGFR mutation–positive NSCLC. The question is how to design trials in a fair and balanced way that doesn’t compromise patient care or ethical standards.

If people think my assessment is too harsh, I openly welcome debate.

Bottom line: The ADAURA trial lays bare deeper problems with clinical trial design, and I would challenge readers to reflect on our clinical trial culture in oncology, which offers a system of rules that rewards denying the best identified care for patients on our clinical trials.

At the very least, should we celebrate these wins without fully acknowledging these problems?
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

A version of this article first appeared on Medscape.com.

Immune checkpoint inhibitors are a cornerstone of non–small cell lung cancer (NSCLC) treatment. But there is a question that’s been vexing oncologists for years: When can treatment be stopped?
 

A new review of clinical trial data suggests that it is safe to stop immunotherapy after 2 years if the patient is progression free. There was no difference in overall survival between such patients and those who carried on with immunotherapy for another 2 years, so for 4 years in total.

“For patients who are progression free on immunotherapy for NSCLC, it is reasonable to stop therapy at 2 years, rather than continuing indefinitely,”  said the investigators, led by medical oncologist Lova Sun, MD, a lung and head and neck cancer specialist at the University of Pennsylvania, Philadelphia.

“The lack of statistically significant overall survival advantage for” indefinite treatment “on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years,” they added.

The study was published online in JAMA Oncology to coincide with a presentation at the annual meeting of the American Society of Clinical Oncology.

Dr. Sun and colleagues commented that there have been a number of trials that have shown durable benefits persisting long after immunotherapy was stopped at 2 years, but clinicians seem to have been spooked into preferring indefinite treatment by a trial that showed worse survival with nivolumab when it was stopped at 1 year in responders versus ongoing treatment.

In an accompanying editorial, Jack West, MD, a medical oncologist and lung cancer specialist at City of Hope, Duarte, Calif., noted that given the “clear limitations in retrospective clinical data, we may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available.

“In the meantime, the perfect should not be the enemy of the good. These data may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same overall survival as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” he said.
 

Study details

For their review, Dr. Sun and colleagues included patients with advanced NSCLC called from 280 cancer clinics from across the United States.

The investigators compared overall survival in 113 advanced NSCLC patients treated with up-front immune checkpoint inhibitors (ICIs) for 700-760 days (that is, stopping within 2 years) with survival in 593 patients treated beyond 760 days (the indefinite therapy group).

Patients were diagnosed from 2016 to 2020 at a median age of 69 years and were about evenly split between the sexes. The team noted that although all the patients were progression free at 2 years, only about one in five discontinued ICIs, highlighting “a strong bias toward potential overtreatment [vs.] possible undertreatment,” as Dr. West put it in the editorial.

Approximately half of the patients in both groups were treated initially with immunotherapy alone and the rest in combination with chemotherapy.

The 2-year overall survival from the 760-day mark was 79% in the fixed-duration group versus 81% with indefinite treatment, with no difference on either univariate (hazard ratio, 1.26; P = .36) or multivariable (HR, 1.33; P = .29) analysis adjusting for smoking history, PD-L1 status, histology, and other covariates.

Eleven patients in the fixed-duration cohort (10%) subsequently had progression and were rechallenged with an ICI; all but one with the same ICI used frontline.

Median progression-free survival after rechallenge was 8.1 months, demonstrating that patients can still benefit from ICIs even after discontinuation, the investigators said.

The groups were well balanced except that patients in the fixed-duration group were more likely to be treated at an academic center and have a history of smoking, with a trend toward being more likely to have squamous cell carcinoma. “Even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” the team said.

There was no funding for the work. The investigators have numerous pharmaceutical industry ties, including Dr. Sun, who is a consultant for Regeneron, Genmab, Seagen, and Bayer, and disclosed funding from BluePrint Research, Seagen Research, and IO Biotech Research. Dr. West reported receiving personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.

A version of this article first appeared on Medscape.com.

Immune checkpoint inhibitors are a cornerstone of non–small cell lung cancer (NSCLC) treatment. But there is a question that’s been vexing oncologists for years: When can treatment be stopped?
 

A new review of clinical trial data suggests that it is safe to stop immunotherapy after 2 years if the patient is progression free. There was no difference in overall survival between such patients and those who carried on with immunotherapy for another 2 years, so for 4 years in total.

“For patients who are progression free on immunotherapy for NSCLC, it is reasonable to stop therapy at 2 years, rather than continuing indefinitely,”  said the investigators, led by medical oncologist Lova Sun, MD, a lung and head and neck cancer specialist at the University of Pennsylvania, Philadelphia.

“The lack of statistically significant overall survival advantage for” indefinite treatment “on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years,” they added.

The study was published online in JAMA Oncology to coincide with a presentation at the annual meeting of the American Society of Clinical Oncology.

Dr. Sun and colleagues commented that there have been a number of trials that have shown durable benefits persisting long after immunotherapy was stopped at 2 years, but clinicians seem to have been spooked into preferring indefinite treatment by a trial that showed worse survival with nivolumab when it was stopped at 1 year in responders versus ongoing treatment.

In an accompanying editorial, Jack West, MD, a medical oncologist and lung cancer specialist at City of Hope, Duarte, Calif., noted that given the “clear limitations in retrospective clinical data, we may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available.

“In the meantime, the perfect should not be the enemy of the good. These data may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same overall survival as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” he said.
 

Study details

For their review, Dr. Sun and colleagues included patients with advanced NSCLC called from 280 cancer clinics from across the United States.

The investigators compared overall survival in 113 advanced NSCLC patients treated with up-front immune checkpoint inhibitors (ICIs) for 700-760 days (that is, stopping within 2 years) with survival in 593 patients treated beyond 760 days (the indefinite therapy group).

Patients were diagnosed from 2016 to 2020 at a median age of 69 years and were about evenly split between the sexes. The team noted that although all the patients were progression free at 2 years, only about one in five discontinued ICIs, highlighting “a strong bias toward potential overtreatment [vs.] possible undertreatment,” as Dr. West put it in the editorial.

Approximately half of the patients in both groups were treated initially with immunotherapy alone and the rest in combination with chemotherapy.

The 2-year overall survival from the 760-day mark was 79% in the fixed-duration group versus 81% with indefinite treatment, with no difference on either univariate (hazard ratio, 1.26; P = .36) or multivariable (HR, 1.33; P = .29) analysis adjusting for smoking history, PD-L1 status, histology, and other covariates.

Eleven patients in the fixed-duration cohort (10%) subsequently had progression and were rechallenged with an ICI; all but one with the same ICI used frontline.

Median progression-free survival after rechallenge was 8.1 months, demonstrating that patients can still benefit from ICIs even after discontinuation, the investigators said.

The groups were well balanced except that patients in the fixed-duration group were more likely to be treated at an academic center and have a history of smoking, with a trend toward being more likely to have squamous cell carcinoma. “Even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” the team said.

There was no funding for the work. The investigators have numerous pharmaceutical industry ties, including Dr. Sun, who is a consultant for Regeneron, Genmab, Seagen, and Bayer, and disclosed funding from BluePrint Research, Seagen Research, and IO Biotech Research. Dr. West reported receiving personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.

A version of this article first appeared on Medscape.com.

Immune checkpoint inhibitors are a cornerstone of non–small cell lung cancer (NSCLC) treatment. But there is a question that’s been vexing oncologists for years: When can treatment be stopped?
 

A new review of clinical trial data suggests that it is safe to stop immunotherapy after 2 years if the patient is progression free. There was no difference in overall survival between such patients and those who carried on with immunotherapy for another 2 years, so for 4 years in total.

“For patients who are progression free on immunotherapy for NSCLC, it is reasonable to stop therapy at 2 years, rather than continuing indefinitely,”  said the investigators, led by medical oncologist Lova Sun, MD, a lung and head and neck cancer specialist at the University of Pennsylvania, Philadelphia.

“The lack of statistically significant overall survival advantage for” indefinite treatment “on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years,” they added.

The study was published online in JAMA Oncology to coincide with a presentation at the annual meeting of the American Society of Clinical Oncology.

Dr. Sun and colleagues commented that there have been a number of trials that have shown durable benefits persisting long after immunotherapy was stopped at 2 years, but clinicians seem to have been spooked into preferring indefinite treatment by a trial that showed worse survival with nivolumab when it was stopped at 1 year in responders versus ongoing treatment.

In an accompanying editorial, Jack West, MD, a medical oncologist and lung cancer specialist at City of Hope, Duarte, Calif., noted that given the “clear limitations in retrospective clinical data, we may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available.

“In the meantime, the perfect should not be the enemy of the good. These data may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same overall survival as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” he said.
 

Study details

For their review, Dr. Sun and colleagues included patients with advanced NSCLC called from 280 cancer clinics from across the United States.

The investigators compared overall survival in 113 advanced NSCLC patients treated with up-front immune checkpoint inhibitors (ICIs) for 700-760 days (that is, stopping within 2 years) with survival in 593 patients treated beyond 760 days (the indefinite therapy group).

Patients were diagnosed from 2016 to 2020 at a median age of 69 years and were about evenly split between the sexes. The team noted that although all the patients were progression free at 2 years, only about one in five discontinued ICIs, highlighting “a strong bias toward potential overtreatment [vs.] possible undertreatment,” as Dr. West put it in the editorial.

Approximately half of the patients in both groups were treated initially with immunotherapy alone and the rest in combination with chemotherapy.

The 2-year overall survival from the 760-day mark was 79% in the fixed-duration group versus 81% with indefinite treatment, with no difference on either univariate (hazard ratio, 1.26; P = .36) or multivariable (HR, 1.33; P = .29) analysis adjusting for smoking history, PD-L1 status, histology, and other covariates.

Eleven patients in the fixed-duration cohort (10%) subsequently had progression and were rechallenged with an ICI; all but one with the same ICI used frontline.

Median progression-free survival after rechallenge was 8.1 months, demonstrating that patients can still benefit from ICIs even after discontinuation, the investigators said.

The groups were well balanced except that patients in the fixed-duration group were more likely to be treated at an academic center and have a history of smoking, with a trend toward being more likely to have squamous cell carcinoma. “Even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” the team said.

There was no funding for the work. The investigators have numerous pharmaceutical industry ties, including Dr. Sun, who is a consultant for Regeneron, Genmab, Seagen, and Bayer, and disclosed funding from BluePrint Research, Seagen Research, and IO Biotech Research. Dr. West reported receiving personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.

A version of this article first appeared on Medscape.com.

CHICAGO – In a phase 1 small cell lung cancer (SCLC) trial, a bispecific antibody that targets T cells and the inhibitory notch ligand known as delta-like ligand 3 (DLL3) showed a good safety profile and encouraging signs of efficacy, including one response that lasted more than a year.

The antibody promotes the destruction of tumor cells by T cells by acting as a bridge between T cells and tumors.

SCLC has largely resisted efforts to identify unique surface markers. DLL3 is an exception: It is rarely expressed in normal cells, and it seems to be important to tumor biology, according to Martin Wermke, MD, who presented the study at the annual meeting of the American Society of Clinical Oncology.
 

A rare SCLC biomarker

“The problem, I think, is that small cell [lung cancer] with its high mutational burden is a bunch of many different subentities and you will probably not find a single driver mutation as you do in non–small cell lung cancer. So in that [way] it’s different in its biology,” said Dr. Wermke, professor of experimental tumor therapy at the National Center for Tumor Diseases in Dresden, Germany.

Nevertheless, DLL3 is a sensitive biomarker, with over 90% of SCLC tumors positive for the surface marker, according to Dr. Wermke. “It’s one of the first which proved to be a reliable [SCLC] biomarker for therapeutic approaches,” said Dr. Wermke.

This isn’t the first clinical experience with DLL3. An anti-DLL3 antibody was used as part of an antibody-drug conjugate called Rova-T, which failed a phase 3 trial in SCLC in 2021 and was subsequently canceled by AbbVie, but Dr. Wermke believes that the issue was with the drug and linker (a chemical tag that links the cytotoxic drug to the antibody, which is designed to release the drug in an appropriate environment such as the interior of a tumor cell after an antibody-drug conjugate has been internalized by the tumor cell), not DLL3. DLL3 is also being investigated as a component of chimeric antigen receptor T-cell therapy, though no clinical results have been reported, Dr. Wermke said.
 

Study methods and results

The study included 107 patients. The median age was 60.0 years, and 57% were male. To be included, patients had to have advanced SCLC, large cell neuroendocrine carcinoma, or extrapulmonary neuroendocrine carcinoma, as well as test positive for DLL3 expression.

The drug was well tolerated: 86% of patients experienced at least one treatment-related adverse event: 59% with a grade 1-2 TRAE and 27% with a grade 3-5 TRAE. Cytokine release syndrome (CRS) occurred in 59% of patients, but just 2% were grade 3-5. TRAEs led to discontinuation in 4% of patients. Physicians were able to manage CRS with supportive care, steroids, and anti–interleukin-6 receptor antibodies.

The treatment showed signs of efficacy, with partial responses occurring in 18% of patients, stable disease in 23%, progressive disease in 45%, while 13% were not evaluable.

At doses of 90 mg/kg or above, partial response occurred in 25% of patients, stable disease in 27%, and progressive disease in 31%, while 13% were not evaluable. Similar patterns were seen across three tumor types.

Of 18 responders, 14 continued to be responders at the time of the presentation. The longest response lengths were 13.1 months, 10.7 months, and 9.4 months.

Dr. Wermke said that the responses were encouraging, particularly the duration of some responses.

“Having a small cell [lung cancer] patient responding to something for more than a year is extraordinary. It comes with side effects, which are usually seen during the first [doses]. After that, the drug is pretty well tolerable, and that is also something which distinguishes it from alternative second-line approaches,” he said.
 

Well tolerated, but take efficacy data with a grain of salt

The study was encouraging but should be treated with caution, according to Vamsidhar Velcheti, MD, who moderated the session where the research was presented.

“The toxicity profile is actually very promising and it’s still very early, but there’s certainly a lot of interest in DLL3-targeted [therapies]. We’ve seen some very exciting data with other assets in this category as well,” said Dr. Velcheti, director of thoracic oncology at NYU Langone Health, New York.

Phase 1 efficacy data can be tantalizing but often fails to hold up to further testing, according to Dr. Velcheti. “We’ve seen signals in phase 1 data before, and we’ve been burned. We saw really promising data with Rova-T, and the confirmatory trials were negative, – so we want to be cautiously optimistic,” said Dr. Velcheti.

He also pointed out that patient selection will be important for such studies, considering that SCLC patients often have a lot of comorbidities and the therapy’s potential for causing CRS.

Both Dr. Wermke and Dr. Velcheti have received funding from numerous pharmaceutical companies. Dr. Wermke has consulted with or advised with Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, ImCheck Therapeutics, Immatics, ISA Pharmaceuticals, Lilly, and Novartis.

CHICAGO – In a phase 1 small cell lung cancer (SCLC) trial, a bispecific antibody that targets T cells and the inhibitory notch ligand known as delta-like ligand 3 (DLL3) showed a good safety profile and encouraging signs of efficacy, including one response that lasted more than a year.

The antibody promotes the destruction of tumor cells by T cells by acting as a bridge between T cells and tumors.

SCLC has largely resisted efforts to identify unique surface markers. DLL3 is an exception: It is rarely expressed in normal cells, and it seems to be important to tumor biology, according to Martin Wermke, MD, who presented the study at the annual meeting of the American Society of Clinical Oncology.
 

A rare SCLC biomarker

“The problem, I think, is that small cell [lung cancer] with its high mutational burden is a bunch of many different subentities and you will probably not find a single driver mutation as you do in non–small cell lung cancer. So in that [way] it’s different in its biology,” said Dr. Wermke, professor of experimental tumor therapy at the National Center for Tumor Diseases in Dresden, Germany.

Nevertheless, DLL3 is a sensitive biomarker, with over 90% of SCLC tumors positive for the surface marker, according to Dr. Wermke. “It’s one of the first which proved to be a reliable [SCLC] biomarker for therapeutic approaches,” said Dr. Wermke.

This isn’t the first clinical experience with DLL3. An anti-DLL3 antibody was used as part of an antibody-drug conjugate called Rova-T, which failed a phase 3 trial in SCLC in 2021 and was subsequently canceled by AbbVie, but Dr. Wermke believes that the issue was with the drug and linker (a chemical tag that links the cytotoxic drug to the antibody, which is designed to release the drug in an appropriate environment such as the interior of a tumor cell after an antibody-drug conjugate has been internalized by the tumor cell), not DLL3. DLL3 is also being investigated as a component of chimeric antigen receptor T-cell therapy, though no clinical results have been reported, Dr. Wermke said.
 

Study methods and results

The study included 107 patients. The median age was 60.0 years, and 57% were male. To be included, patients had to have advanced SCLC, large cell neuroendocrine carcinoma, or extrapulmonary neuroendocrine carcinoma, as well as test positive for DLL3 expression.

The drug was well tolerated: 86% of patients experienced at least one treatment-related adverse event: 59% with a grade 1-2 TRAE and 27% with a grade 3-5 TRAE. Cytokine release syndrome (CRS) occurred in 59% of patients, but just 2% were grade 3-5. TRAEs led to discontinuation in 4% of patients. Physicians were able to manage CRS with supportive care, steroids, and anti–interleukin-6 receptor antibodies.

The treatment showed signs of efficacy, with partial responses occurring in 18% of patients, stable disease in 23%, progressive disease in 45%, while 13% were not evaluable.

At doses of 90 mg/kg or above, partial response occurred in 25% of patients, stable disease in 27%, and progressive disease in 31%, while 13% were not evaluable. Similar patterns were seen across three tumor types.

Of 18 responders, 14 continued to be responders at the time of the presentation. The longest response lengths were 13.1 months, 10.7 months, and 9.4 months.

Dr. Wermke said that the responses were encouraging, particularly the duration of some responses.

“Having a small cell [lung cancer] patient responding to something for more than a year is extraordinary. It comes with side effects, which are usually seen during the first [doses]. After that, the drug is pretty well tolerable, and that is also something which distinguishes it from alternative second-line approaches,” he said.
 

Well tolerated, but take efficacy data with a grain of salt

The study was encouraging but should be treated with caution, according to Vamsidhar Velcheti, MD, who moderated the session where the research was presented.

“The toxicity profile is actually very promising and it’s still very early, but there’s certainly a lot of interest in DLL3-targeted [therapies]. We’ve seen some very exciting data with other assets in this category as well,” said Dr. Velcheti, director of thoracic oncology at NYU Langone Health, New York.

Phase 1 efficacy data can be tantalizing but often fails to hold up to further testing, according to Dr. Velcheti. “We’ve seen signals in phase 1 data before, and we’ve been burned. We saw really promising data with Rova-T, and the confirmatory trials were negative, – so we want to be cautiously optimistic,” said Dr. Velcheti.

He also pointed out that patient selection will be important for such studies, considering that SCLC patients often have a lot of comorbidities and the therapy’s potential for causing CRS.

Both Dr. Wermke and Dr. Velcheti have received funding from numerous pharmaceutical companies. Dr. Wermke has consulted with or advised with Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, ImCheck Therapeutics, Immatics, ISA Pharmaceuticals, Lilly, and Novartis.

CHICAGO – In a phase 1 small cell lung cancer (SCLC) trial, a bispecific antibody that targets T cells and the inhibitory notch ligand known as delta-like ligand 3 (DLL3) showed a good safety profile and encouraging signs of efficacy, including one response that lasted more than a year.

The antibody promotes the destruction of tumor cells by T cells by acting as a bridge between T cells and tumors.

SCLC has largely resisted efforts to identify unique surface markers. DLL3 is an exception: It is rarely expressed in normal cells, and it seems to be important to tumor biology, according to Martin Wermke, MD, who presented the study at the annual meeting of the American Society of Clinical Oncology.
 

A rare SCLC biomarker

“The problem, I think, is that small cell [lung cancer] with its high mutational burden is a bunch of many different subentities and you will probably not find a single driver mutation as you do in non–small cell lung cancer. So in that [way] it’s different in its biology,” said Dr. Wermke, professor of experimental tumor therapy at the National Center for Tumor Diseases in Dresden, Germany.

Nevertheless, DLL3 is a sensitive biomarker, with over 90% of SCLC tumors positive for the surface marker, according to Dr. Wermke. “It’s one of the first which proved to be a reliable [SCLC] biomarker for therapeutic approaches,” said Dr. Wermke.

This isn’t the first clinical experience with DLL3. An anti-DLL3 antibody was used as part of an antibody-drug conjugate called Rova-T, which failed a phase 3 trial in SCLC in 2021 and was subsequently canceled by AbbVie, but Dr. Wermke believes that the issue was with the drug and linker (a chemical tag that links the cytotoxic drug to the antibody, which is designed to release the drug in an appropriate environment such as the interior of a tumor cell after an antibody-drug conjugate has been internalized by the tumor cell), not DLL3. DLL3 is also being investigated as a component of chimeric antigen receptor T-cell therapy, though no clinical results have been reported, Dr. Wermke said.
 

Study methods and results

The study included 107 patients. The median age was 60.0 years, and 57% were male. To be included, patients had to have advanced SCLC, large cell neuroendocrine carcinoma, or extrapulmonary neuroendocrine carcinoma, as well as test positive for DLL3 expression.

The drug was well tolerated: 86% of patients experienced at least one treatment-related adverse event: 59% with a grade 1-2 TRAE and 27% with a grade 3-5 TRAE. Cytokine release syndrome (CRS) occurred in 59% of patients, but just 2% were grade 3-5. TRAEs led to discontinuation in 4% of patients. Physicians were able to manage CRS with supportive care, steroids, and anti–interleukin-6 receptor antibodies.

The treatment showed signs of efficacy, with partial responses occurring in 18% of patients, stable disease in 23%, progressive disease in 45%, while 13% were not evaluable.

At doses of 90 mg/kg or above, partial response occurred in 25% of patients, stable disease in 27%, and progressive disease in 31%, while 13% were not evaluable. Similar patterns were seen across three tumor types.

Of 18 responders, 14 continued to be responders at the time of the presentation. The longest response lengths were 13.1 months, 10.7 months, and 9.4 months.

Dr. Wermke said that the responses were encouraging, particularly the duration of some responses.

“Having a small cell [lung cancer] patient responding to something for more than a year is extraordinary. It comes with side effects, which are usually seen during the first [doses]. After that, the drug is pretty well tolerable, and that is also something which distinguishes it from alternative second-line approaches,” he said.
 

Well tolerated, but take efficacy data with a grain of salt

The study was encouraging but should be treated with caution, according to Vamsidhar Velcheti, MD, who moderated the session where the research was presented.

“The toxicity profile is actually very promising and it’s still very early, but there’s certainly a lot of interest in DLL3-targeted [therapies]. We’ve seen some very exciting data with other assets in this category as well,” said Dr. Velcheti, director of thoracic oncology at NYU Langone Health, New York.

Phase 1 efficacy data can be tantalizing but often fails to hold up to further testing, according to Dr. Velcheti. “We’ve seen signals in phase 1 data before, and we’ve been burned. We saw really promising data with Rova-T, and the confirmatory trials were negative, – so we want to be cautiously optimistic,” said Dr. Velcheti.

He also pointed out that patient selection will be important for such studies, considering that SCLC patients often have a lot of comorbidities and the therapy’s potential for causing CRS.

Both Dr. Wermke and Dr. Velcheti have received funding from numerous pharmaceutical companies. Dr. Wermke has consulted with or advised with Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, ImCheck Therapeutics, Immatics, ISA Pharmaceuticals, Lilly, and Novartis.