Federal Practitioner

A type of B-cell lymphoma called early-stage I primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) has highly favorable survival rates, according to new research presented at the European Society of Medical Oncology (ESMO) Congress 2023. While relapse is common, those rates are significantly lower with radiation therapy.

“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.

Dr. Gao presented these findings at ESMO 2023, held in Madrid.

“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”

POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.

Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.

“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.

To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.

Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.

Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.

With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.

Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.

The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).

In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.

“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.

Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).

The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).

However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.

Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.

Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.

Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.

In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.

“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.

“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.

“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”

Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”


 

Benefits linked to radiation therapy dose?

Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.

“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.

The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”

He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”

Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”

The authors had no disclosures to report.

A type of B-cell lymphoma called early-stage I primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) has highly favorable survival rates, according to new research presented at the European Society of Medical Oncology (ESMO) Congress 2023. While relapse is common, those rates are significantly lower with radiation therapy.

“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.

Dr. Gao presented these findings at ESMO 2023, held in Madrid.

“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”

POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.

Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.

“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.

To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.

Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.

Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.

With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.

Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.

The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).

In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.

“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.

Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).

The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).

However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.

Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.

Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.

Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.

In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.

“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.

“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.

“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”

Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”


 

Benefits linked to radiation therapy dose?

Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.

“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.

The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”

He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”

Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”

The authors had no disclosures to report.

A type of B-cell lymphoma called early-stage I primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) has highly favorable survival rates, according to new research presented at the European Society of Medical Oncology (ESMO) Congress 2023. While relapse is common, those rates are significantly lower with radiation therapy.

“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.

Dr. Gao presented these findings at ESMO 2023, held in Madrid.

“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”

POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.

Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.

“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.

To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.

Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.

Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.

With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.

Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.

The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).

In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.

“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.

Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).

The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).

However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.

Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.

Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.

Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.

In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.

“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.

“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.

“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”

Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”


 

Benefits linked to radiation therapy dose?

Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.

“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.

The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”

He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”

Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”

The authors had no disclosures to report.

Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers. 

A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?

Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery. 

“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.

Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care. 

“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”

With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
 

Not so fast in the United States

In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal. 

Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.

“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”

States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.

But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.

Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.

The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.

For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.

This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.

“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease. 

For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors. 

A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.

Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said. 
 

Changes in the United States

The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases. 

The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.

But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said. 

“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”

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

Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers. 

A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?

Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery. 

“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.

Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care. 

“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”

With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
 

Not so fast in the United States

In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal. 

Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.

“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”

States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.

But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.

Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.

The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.

For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.

This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.

“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease. 

For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors. 

A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.

Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said. 
 

Changes in the United States

The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases. 

The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.

But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said. 

“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”

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

Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers. 

A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?

Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery. 

“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.

Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care. 

“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”

With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
 

Not so fast in the United States

In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal. 

Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.

“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”

States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.

But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.

Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.

The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.

For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.

This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.

“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease. 

For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors. 

A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.

Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said. 
 

Changes in the United States

The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases. 

The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.

But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said. 

“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”

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

NEW YORK – In the last 25 years, major advances in treating multiple myeloma (MM) have doubled survival rates, yet the still incurable disease often requires lifelong maintenance therapy. Since CAR T-cell therapy has emerged as a viable strategy to prolong survival and deepen response in relapsed or refractory (RR) patients, the question arises: Should CAR T replace autologous stem cell transplant (ASCT) in earlier lines of treatment?

courtesy MSKCC

“In an otherwise healthy treatment-naive patient with multiple myeloma, to ensure the best chances of overall survival, I would always recommend standard of care consolidation therapy of chemotherapy + ASCT,” said Sergio Giralt, MD, of New York’s Memorial Sloan Kettering Cancer Center, debating the merits of ASCT versus CAR T as consolidation therapy at the Lymphoma, Leukemia & Myeloma (LLM) Congress 2023 in New York.

Final results from the phase II GRIFFIN trial highlight the benchmarks that CAR T-cell therapy would need to reach to achieve equivalence with ASCT. At a 4-year follow-up, newly diagnosed MM patients who received daratumumab, lenalidomide, bortezomib, and dexamethasone (D-RVd) followed by ASCT + D-RVd consolidation, and daratumumab maintenance, had a progression-free survival (PFS) rate of 87.3%, 92.7% overall survival (OS) rate, and 50% achieved minimal residual disease negativity.

Dr. Adriana Rossi, MD, assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York, cited a convergence of evidence suggesting that CAR T could achieve impressive results as a consolidation therapy in fit patients with MM, including: CARTITUDE 1 and CARTITUDE 4, which studied CAR T in RR MM patients. However, due to the fact that no head-to-head study of CAR T vs. ASCT as consolidation therapy in otherwise healthy MM patients exists, “There is not enough long-term data to support the equivalence CAR T with ASCT,” Dr. Giralt concluded.

Dr. Rossi further advocated for considering CAR T as a consolidation treatment because of the risks of secondary malignancies associated with ACST maintenance regimens.

Dr. Giralt rebutted this argument by citing data about averse events (AE) in studies of CAR-T therapies in RR MM patients like KarMMa-2, in which grade 3-4 neutropenia, anemia, and thrombocytopenia occurred in 94.6%, 45.9%, and 37.8% of patients respectively. Furthermore, 2 of 37 patients in KarMMA died (1 pneumonia, 1 pseudomonal sepsis), while rates of death from AEs related to ASCT occur in less than 1% of patients, according to Dr. Giralt.

Beyond a dearth of evidence thus far about the long term PFS, OS, and safety profile superiority of CAR-T therapies, compared with ASCT in treatment-naive MM patients, Dr. Giralt also noted the facts that CAR T-cell therapies are expensive and require manufacturing infrastructure also demonstrate that they cannot be easily adopted everywhere, even as a third-line therapy.

“In many places like Morocco, where I practice, we do not have access to CAR-T therapies,” said Sadia Zafad, MD, of the Clinique Al Madina Hematology and Oncology Center in Casablanca, Morocco. Dr. Zafad attended the debate.

A lack of access to CAR T is also a problem in the United States, where wait times for the therapy can stretch up to 6 months, getting insurance approval is challenging, and many patients simply don’t live near a center where CAR T-cell therapy is available. Citing all these factors, Dr. Giralt concluded: “Even if CAR T can be shown to have the same results as transplant, it is much more resource-intensive than transplant, and insurers are going to start saying there’s no necessary benefit. We have yet to use value as a primary end point, but as cancer care gets more and more expensive, that’s going to come up more, for CAR T and other novel therapies.”

Dr. Giralt reported relationships with Actinuum, Amgen, BMS, Celgene, Crisper, J&J, Jazz, Kite, Miltenyi, Novartis, Sanofi, and Takeda. Dr. Rossi disclosed ties with Adaptive, BMS, Celgene, JNJ, Sanofi & Genzyme. Dr. Zafad reported no disclosures.

NEW YORK – In the last 25 years, major advances in treating multiple myeloma (MM) have doubled survival rates, yet the still incurable disease often requires lifelong maintenance therapy. Since CAR T-cell therapy has emerged as a viable strategy to prolong survival and deepen response in relapsed or refractory (RR) patients, the question arises: Should CAR T replace autologous stem cell transplant (ASCT) in earlier lines of treatment?

courtesy MSKCC

“In an otherwise healthy treatment-naive patient with multiple myeloma, to ensure the best chances of overall survival, I would always recommend standard of care consolidation therapy of chemotherapy + ASCT,” said Sergio Giralt, MD, of New York’s Memorial Sloan Kettering Cancer Center, debating the merits of ASCT versus CAR T as consolidation therapy at the Lymphoma, Leukemia & Myeloma (LLM) Congress 2023 in New York.

Final results from the phase II GRIFFIN trial highlight the benchmarks that CAR T-cell therapy would need to reach to achieve equivalence with ASCT. At a 4-year follow-up, newly diagnosed MM patients who received daratumumab, lenalidomide, bortezomib, and dexamethasone (D-RVd) followed by ASCT + D-RVd consolidation, and daratumumab maintenance, had a progression-free survival (PFS) rate of 87.3%, 92.7% overall survival (OS) rate, and 50% achieved minimal residual disease negativity.

Dr. Adriana Rossi, MD, assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York, cited a convergence of evidence suggesting that CAR T could achieve impressive results as a consolidation therapy in fit patients with MM, including: CARTITUDE 1 and CARTITUDE 4, which studied CAR T in RR MM patients. However, due to the fact that no head-to-head study of CAR T vs. ASCT as consolidation therapy in otherwise healthy MM patients exists, “There is not enough long-term data to support the equivalence CAR T with ASCT,” Dr. Giralt concluded.

Dr. Rossi further advocated for considering CAR T as a consolidation treatment because of the risks of secondary malignancies associated with ACST maintenance regimens.

Dr. Giralt rebutted this argument by citing data about averse events (AE) in studies of CAR-T therapies in RR MM patients like KarMMa-2, in which grade 3-4 neutropenia, anemia, and thrombocytopenia occurred in 94.6%, 45.9%, and 37.8% of patients respectively. Furthermore, 2 of 37 patients in KarMMA died (1 pneumonia, 1 pseudomonal sepsis), while rates of death from AEs related to ASCT occur in less than 1% of patients, according to Dr. Giralt.

Beyond a dearth of evidence thus far about the long term PFS, OS, and safety profile superiority of CAR-T therapies, compared with ASCT in treatment-naive MM patients, Dr. Giralt also noted the facts that CAR T-cell therapies are expensive and require manufacturing infrastructure also demonstrate that they cannot be easily adopted everywhere, even as a third-line therapy.

“In many places like Morocco, where I practice, we do not have access to CAR-T therapies,” said Sadia Zafad, MD, of the Clinique Al Madina Hematology and Oncology Center in Casablanca, Morocco. Dr. Zafad attended the debate.

A lack of access to CAR T is also a problem in the United States, where wait times for the therapy can stretch up to 6 months, getting insurance approval is challenging, and many patients simply don’t live near a center where CAR T-cell therapy is available. Citing all these factors, Dr. Giralt concluded: “Even if CAR T can be shown to have the same results as transplant, it is much more resource-intensive than transplant, and insurers are going to start saying there’s no necessary benefit. We have yet to use value as a primary end point, but as cancer care gets more and more expensive, that’s going to come up more, for CAR T and other novel therapies.”

Dr. Giralt reported relationships with Actinuum, Amgen, BMS, Celgene, Crisper, J&J, Jazz, Kite, Miltenyi, Novartis, Sanofi, and Takeda. Dr. Rossi disclosed ties with Adaptive, BMS, Celgene, JNJ, Sanofi & Genzyme. Dr. Zafad reported no disclosures.

NEW YORK – In the last 25 years, major advances in treating multiple myeloma (MM) have doubled survival rates, yet the still incurable disease often requires lifelong maintenance therapy. Since CAR T-cell therapy has emerged as a viable strategy to prolong survival and deepen response in relapsed or refractory (RR) patients, the question arises: Should CAR T replace autologous stem cell transplant (ASCT) in earlier lines of treatment?

courtesy MSKCC

“In an otherwise healthy treatment-naive patient with multiple myeloma, to ensure the best chances of overall survival, I would always recommend standard of care consolidation therapy of chemotherapy + ASCT,” said Sergio Giralt, MD, of New York’s Memorial Sloan Kettering Cancer Center, debating the merits of ASCT versus CAR T as consolidation therapy at the Lymphoma, Leukemia & Myeloma (LLM) Congress 2023 in New York.

Final results from the phase II GRIFFIN trial highlight the benchmarks that CAR T-cell therapy would need to reach to achieve equivalence with ASCT. At a 4-year follow-up, newly diagnosed MM patients who received daratumumab, lenalidomide, bortezomib, and dexamethasone (D-RVd) followed by ASCT + D-RVd consolidation, and daratumumab maintenance, had a progression-free survival (PFS) rate of 87.3%, 92.7% overall survival (OS) rate, and 50% achieved minimal residual disease negativity.

Dr. Adriana Rossi, MD, assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York, cited a convergence of evidence suggesting that CAR T could achieve impressive results as a consolidation therapy in fit patients with MM, including: CARTITUDE 1 and CARTITUDE 4, which studied CAR T in RR MM patients. However, due to the fact that no head-to-head study of CAR T vs. ASCT as consolidation therapy in otherwise healthy MM patients exists, “There is not enough long-term data to support the equivalence CAR T with ASCT,” Dr. Giralt concluded.

Dr. Rossi further advocated for considering CAR T as a consolidation treatment because of the risks of secondary malignancies associated with ACST maintenance regimens.

Dr. Giralt rebutted this argument by citing data about averse events (AE) in studies of CAR-T therapies in RR MM patients like KarMMa-2, in which grade 3-4 neutropenia, anemia, and thrombocytopenia occurred in 94.6%, 45.9%, and 37.8% of patients respectively. Furthermore, 2 of 37 patients in KarMMA died (1 pneumonia, 1 pseudomonal sepsis), while rates of death from AEs related to ASCT occur in less than 1% of patients, according to Dr. Giralt.

Beyond a dearth of evidence thus far about the long term PFS, OS, and safety profile superiority of CAR-T therapies, compared with ASCT in treatment-naive MM patients, Dr. Giralt also noted the facts that CAR T-cell therapies are expensive and require manufacturing infrastructure also demonstrate that they cannot be easily adopted everywhere, even as a third-line therapy.

“In many places like Morocco, where I practice, we do not have access to CAR-T therapies,” said Sadia Zafad, MD, of the Clinique Al Madina Hematology and Oncology Center in Casablanca, Morocco. Dr. Zafad attended the debate.

A lack of access to CAR T is also a problem in the United States, where wait times for the therapy can stretch up to 6 months, getting insurance approval is challenging, and many patients simply don’t live near a center where CAR T-cell therapy is available. Citing all these factors, Dr. Giralt concluded: “Even if CAR T can be shown to have the same results as transplant, it is much more resource-intensive than transplant, and insurers are going to start saying there’s no necessary benefit. We have yet to use value as a primary end point, but as cancer care gets more and more expensive, that’s going to come up more, for CAR T and other novel therapies.”

Dr. Giralt reported relationships with Actinuum, Amgen, BMS, Celgene, Crisper, J&J, Jazz, Kite, Miltenyi, Novartis, Sanofi, and Takeda. Dr. Rossi disclosed ties with Adaptive, BMS, Celgene, JNJ, Sanofi & Genzyme. Dr. Zafad reported no disclosures.

More than 1 in 10 Americans over age 60 years will be diagnosed with cancer, according to the National Cancer Institute, making screening for the disease in older patients imperative. Much of the burden of cancer screening falls on primary care physicians. This news organization spoke recently with William L. Dahut, MD, chief scientific officer of the American Cancer Society, about the particular challenges of screening in older patients.

Question: How much does cancer screening change with age? What are the considerations for clinicians – what risks and comorbidities are important to consider in older populations?

Answer: We at the American Cancer Society are giving a lot of thought to how to help primary care practices keep up with screening, particularly with respect to guidelines, but also best practices where judgment is required, such as cancer screening in their older patients.

We’ve had a lot of conversations recently about cancer risk in the young, largely because data show rates are going up for colorectal and breast cancer in this population. But it’s not one size fits all. Screening for young women who have a BRCA gene, if they have dense breasts, or if they have a strong family history of breast cancer should be different from those who are at average risk of the disease.

But statistically, there are about 15 per 100,000 breast cancer diagnoses in women under the age of 40 while over the age of 65 it’s 443 per 100,000. So, the risk significantly increases with age but we should not have an arbitrary cut-off. The life expectancy of a woman at age 75 is about 13.5 years. If you’re over the age of 70 or 75, then it’s going to be comorbidities that you look at, as well as individual patient decisions. Patients may say, “I don’t want to ever go through a mammogram again, because I don’t want to have a biopsy again, and I’m not going to get treated.” Or they may say, “My mom died of metastatic breast cancer when she was 82 and I want to know.”
 

Q: How should primary care physicians interpret conflicting guidance from the major medical groups? For example, the American College of Gastroenterology and your own organization recommend colorectal cancer screening start at age 45 now. But the American College of Physicians recently came out and said 50. What is a well-meaning primary care physician supposed to do?

A: We make more of guideline differences than we should. Sometimes guideline differences aren’t a reflection of different judgments, but rather what data were available when the most recent update took place. For colorectal cancer screening, the ACS dropped the age to begin screening to 45 in 2018 based on a very careful consideration of disease burden data and within several years most other guideline developers reached the same conclusion.

However, I think it’s good for family practice and internal medicine doctors to know that significant GI symptoms in a young patient could be colorectal cancer. It’s not as if nobody sees a 34-year-old or 27-year-old with colorectal cancer. They should be aware that if something goes away in a day or two, that’s fine, but persistent GI symptoms need a cancer workup – colonoscopy or referral to a gastroenterologist. So that’s why I think age 45 is the time when folks should begin screening.
 

Q: What are the medical-legal issues for a physician who is trying to follow guideline-based care when there are different guidelines?

A: Any physician can say, “We follow the guidelines of this particular organization.” I don’t think anyone can say that an organization’s guidelines are malpractice. For individual physicians, following a set of office-based guidelines will hopefully keep them out of legal difficulty.

Q: What are the risks of overscreening, especially in breast cancer where false positives may result in invasive testing?

A: What people think of as overscreening takes a number of different forms. What one guideline would imply is overscreening is recommended screening by another guideline. I think we would all agree that in an average-risk population, beginning screening before it is recommended would be overscreening, and continuing screening when a patient has life-limiting comorbidities would constitute overscreening. Screening too frequently can constitute overscreening.

For example, many women report that their doctors still are advising a baseline mammogram at age 35. Most guideline-developing organizations would regard this as overscreening in an average-risk population.

I think we are also getting better, certainly in prostate cancer, about knowing who needs to be treated and not treated. There are a lot of cancers that would have been treated 20-30 years ago but now are being safely followed with PSA and MRI. We may be able to get to that point with breast cancer over time, too.
 

Q: Are you saying that there may be breast cancers for which active surveillance is appropriate? Is that already the case?

A: We’re not there yet. I think some of the DCIS breast cancers are part of the discussion on whether hormonal treatment or surgeries are done. I think people do have those discussions in the context of morbidity and life expectancy. Over time, we’re likely to have more cancers for which we won’t need surgical treatments.
 

Q: Why did the American Cancer Society change the upper limit for lung cancer screening from 75 to 80 years of age?

 A: For an individual older than 65, screening will now continue until the patient is 80, assuming the patient is in good health. According to the previous guideline, if a patient was 65 and more than 15 years beyond smoking cessation, then screening would end. This is exactly the time when we see lung cancers increase in the population and so a curable lung cancer would not previously have been detected by a screening CT scan. *  

Q: What role do the multicancer blood and DNA tests play in screening now?

A: As you know, the Exact Sciences Cologuard test is already included in major guidelines for colorectal cancer screening and covered by insurance. Our philosophy on multicancer early detection tests is that we’re supportive of Medicare reimbursement when two things occur: 1. When we know there’s clinical benefit, and 2. When the test has been approved by the FDA.

The multicancer early detection tests in development and undergoing prospective research would not now replace screening for the cancers with established screening programs, but if they are shown to have clinical utility for the cancers in their panel, we would be able to reduce deaths from cancers that mostly are diagnosed at late stages and have poor prognoses.

There’s going to be a need for expertise in primary care practices to help interpret the tests. These are new questions, which are well beyond what even the typical oncologist is trained in, much less primary care physicians. We and other organizations are working on providing those answers.
 

Q: While we’re on the subject of the future, how do you envision AI helping or hindering cancer screening specifically in primary care?

A: I think AI is going to help things for a couple of reasons. The ability of AI is to get through data quickly and get you information that’s personalized and useful. If AI tools could let a patient know their individual risk of a cancer in the near and long term, that would help the primary care doctor screen in an individualized way. I think AI is going to be able to improve both diagnostic radiology and pathology, and could make a very big difference in settings outside of large cancer centers that operate at high volume every day. The data look very promising for AI to contribute to risk estimation by operating like a second reader in imaging and pathology.
 

Q: Anything else you’d like to say on this subject that clinicians should know?

A: The questions about whether or not patients should be screened is being pushed on family practice doctors and internists and these questions require a relationship with the patient. A hard stopping point at age 70 when lots of people will live 20 years or more doesn’t make sense.

There’s very little data from randomized clinical trials of screening people over the age of 70. We know that cancer risk does obviously increase with age, particularly prostate and breast cancer. And these are the cancers that are going to be the most common in your practices. If someone has a known mutation, I think you’re going to look differently at screening them. And first-degree family members, particularly for the more aggressive cancers, should be considered for screening.

My philosophy on cancer screening in the elderly is that I think the guidelines are guidelines. If patients have very limited life expectancy, then they shouldn’t be screened. There are calculators that estimate life expectancy in the context of current age and current health status, and these can be useful for decision making and counseling. Patients never think their life expectancy is shorter than 10 years. If their life expectancy is longer than 10 years, then I think, all things being equal, they should continue screening, but the question of ongoing screening needs to be periodically revisited.

*This story was updated on Nov. 1, 2023.
 

More than 1 in 10 Americans over age 60 years will be diagnosed with cancer, according to the National Cancer Institute, making screening for the disease in older patients imperative. Much of the burden of cancer screening falls on primary care physicians. This news organization spoke recently with William L. Dahut, MD, chief scientific officer of the American Cancer Society, about the particular challenges of screening in older patients.

Question: How much does cancer screening change with age? What are the considerations for clinicians – what risks and comorbidities are important to consider in older populations?

Answer: We at the American Cancer Society are giving a lot of thought to how to help primary care practices keep up with screening, particularly with respect to guidelines, but also best practices where judgment is required, such as cancer screening in their older patients.

We’ve had a lot of conversations recently about cancer risk in the young, largely because data show rates are going up for colorectal and breast cancer in this population. But it’s not one size fits all. Screening for young women who have a BRCA gene, if they have dense breasts, or if they have a strong family history of breast cancer should be different from those who are at average risk of the disease.

But statistically, there are about 15 per 100,000 breast cancer diagnoses in women under the age of 40 while over the age of 65 it’s 443 per 100,000. So, the risk significantly increases with age but we should not have an arbitrary cut-off. The life expectancy of a woman at age 75 is about 13.5 years. If you’re over the age of 70 or 75, then it’s going to be comorbidities that you look at, as well as individual patient decisions. Patients may say, “I don’t want to ever go through a mammogram again, because I don’t want to have a biopsy again, and I’m not going to get treated.” Or they may say, “My mom died of metastatic breast cancer when she was 82 and I want to know.”
 

Q: How should primary care physicians interpret conflicting guidance from the major medical groups? For example, the American College of Gastroenterology and your own organization recommend colorectal cancer screening start at age 45 now. But the American College of Physicians recently came out and said 50. What is a well-meaning primary care physician supposed to do?

A: We make more of guideline differences than we should. Sometimes guideline differences aren’t a reflection of different judgments, but rather what data were available when the most recent update took place. For colorectal cancer screening, the ACS dropped the age to begin screening to 45 in 2018 based on a very careful consideration of disease burden data and within several years most other guideline developers reached the same conclusion.

However, I think it’s good for family practice and internal medicine doctors to know that significant GI symptoms in a young patient could be colorectal cancer. It’s not as if nobody sees a 34-year-old or 27-year-old with colorectal cancer. They should be aware that if something goes away in a day or two, that’s fine, but persistent GI symptoms need a cancer workup – colonoscopy or referral to a gastroenterologist. So that’s why I think age 45 is the time when folks should begin screening.
 

Q: What are the medical-legal issues for a physician who is trying to follow guideline-based care when there are different guidelines?

A: Any physician can say, “We follow the guidelines of this particular organization.” I don’t think anyone can say that an organization’s guidelines are malpractice. For individual physicians, following a set of office-based guidelines will hopefully keep them out of legal difficulty.

Q: What are the risks of overscreening, especially in breast cancer where false positives may result in invasive testing?

A: What people think of as overscreening takes a number of different forms. What one guideline would imply is overscreening is recommended screening by another guideline. I think we would all agree that in an average-risk population, beginning screening before it is recommended would be overscreening, and continuing screening when a patient has life-limiting comorbidities would constitute overscreening. Screening too frequently can constitute overscreening.

For example, many women report that their doctors still are advising a baseline mammogram at age 35. Most guideline-developing organizations would regard this as overscreening in an average-risk population.

I think we are also getting better, certainly in prostate cancer, about knowing who needs to be treated and not treated. There are a lot of cancers that would have been treated 20-30 years ago but now are being safely followed with PSA and MRI. We may be able to get to that point with breast cancer over time, too.
 

Q: Are you saying that there may be breast cancers for which active surveillance is appropriate? Is that already the case?

A: We’re not there yet. I think some of the DCIS breast cancers are part of the discussion on whether hormonal treatment or surgeries are done. I think people do have those discussions in the context of morbidity and life expectancy. Over time, we’re likely to have more cancers for which we won’t need surgical treatments.
 

Q: Why did the American Cancer Society change the upper limit for lung cancer screening from 75 to 80 years of age?

 A: For an individual older than 65, screening will now continue until the patient is 80, assuming the patient is in good health. According to the previous guideline, if a patient was 65 and more than 15 years beyond smoking cessation, then screening would end. This is exactly the time when we see lung cancers increase in the population and so a curable lung cancer would not previously have been detected by a screening CT scan. *  

Q: What role do the multicancer blood and DNA tests play in screening now?

A: As you know, the Exact Sciences Cologuard test is already included in major guidelines for colorectal cancer screening and covered by insurance. Our philosophy on multicancer early detection tests is that we’re supportive of Medicare reimbursement when two things occur: 1. When we know there’s clinical benefit, and 2. When the test has been approved by the FDA.

The multicancer early detection tests in development and undergoing prospective research would not now replace screening for the cancers with established screening programs, but if they are shown to have clinical utility for the cancers in their panel, we would be able to reduce deaths from cancers that mostly are diagnosed at late stages and have poor prognoses.

There’s going to be a need for expertise in primary care practices to help interpret the tests. These are new questions, which are well beyond what even the typical oncologist is trained in, much less primary care physicians. We and other organizations are working on providing those answers.
 

Q: While we’re on the subject of the future, how do you envision AI helping or hindering cancer screening specifically in primary care?

A: I think AI is going to help things for a couple of reasons. The ability of AI is to get through data quickly and get you information that’s personalized and useful. If AI tools could let a patient know their individual risk of a cancer in the near and long term, that would help the primary care doctor screen in an individualized way. I think AI is going to be able to improve both diagnostic radiology and pathology, and could make a very big difference in settings outside of large cancer centers that operate at high volume every day. The data look very promising for AI to contribute to risk estimation by operating like a second reader in imaging and pathology.
 

Q: Anything else you’d like to say on this subject that clinicians should know?

A: The questions about whether or not patients should be screened is being pushed on family practice doctors and internists and these questions require a relationship with the patient. A hard stopping point at age 70 when lots of people will live 20 years or more doesn’t make sense.

There’s very little data from randomized clinical trials of screening people over the age of 70. We know that cancer risk does obviously increase with age, particularly prostate and breast cancer. And these are the cancers that are going to be the most common in your practices. If someone has a known mutation, I think you’re going to look differently at screening them. And first-degree family members, particularly for the more aggressive cancers, should be considered for screening.

My philosophy on cancer screening in the elderly is that I think the guidelines are guidelines. If patients have very limited life expectancy, then they shouldn’t be screened. There are calculators that estimate life expectancy in the context of current age and current health status, and these can be useful for decision making and counseling. Patients never think their life expectancy is shorter than 10 years. If their life expectancy is longer than 10 years, then I think, all things being equal, they should continue screening, but the question of ongoing screening needs to be periodically revisited.

*This story was updated on Nov. 1, 2023.
 

More than 1 in 10 Americans over age 60 years will be diagnosed with cancer, according to the National Cancer Institute, making screening for the disease in older patients imperative. Much of the burden of cancer screening falls on primary care physicians. This news organization spoke recently with William L. Dahut, MD, chief scientific officer of the American Cancer Society, about the particular challenges of screening in older patients.

Question: How much does cancer screening change with age? What are the considerations for clinicians – what risks and comorbidities are important to consider in older populations?

Answer: We at the American Cancer Society are giving a lot of thought to how to help primary care practices keep up with screening, particularly with respect to guidelines, but also best practices where judgment is required, such as cancer screening in their older patients.

We’ve had a lot of conversations recently about cancer risk in the young, largely because data show rates are going up for colorectal and breast cancer in this population. But it’s not one size fits all. Screening for young women who have a BRCA gene, if they have dense breasts, or if they have a strong family history of breast cancer should be different from those who are at average risk of the disease.

But statistically, there are about 15 per 100,000 breast cancer diagnoses in women under the age of 40 while over the age of 65 it’s 443 per 100,000. So, the risk significantly increases with age but we should not have an arbitrary cut-off. The life expectancy of a woman at age 75 is about 13.5 years. If you’re over the age of 70 or 75, then it’s going to be comorbidities that you look at, as well as individual patient decisions. Patients may say, “I don’t want to ever go through a mammogram again, because I don’t want to have a biopsy again, and I’m not going to get treated.” Or they may say, “My mom died of metastatic breast cancer when she was 82 and I want to know.”
 

Q: How should primary care physicians interpret conflicting guidance from the major medical groups? For example, the American College of Gastroenterology and your own organization recommend colorectal cancer screening start at age 45 now. But the American College of Physicians recently came out and said 50. What is a well-meaning primary care physician supposed to do?

A: We make more of guideline differences than we should. Sometimes guideline differences aren’t a reflection of different judgments, but rather what data were available when the most recent update took place. For colorectal cancer screening, the ACS dropped the age to begin screening to 45 in 2018 based on a very careful consideration of disease burden data and within several years most other guideline developers reached the same conclusion.

However, I think it’s good for family practice and internal medicine doctors to know that significant GI symptoms in a young patient could be colorectal cancer. It’s not as if nobody sees a 34-year-old or 27-year-old with colorectal cancer. They should be aware that if something goes away in a day or two, that’s fine, but persistent GI symptoms need a cancer workup – colonoscopy or referral to a gastroenterologist. So that’s why I think age 45 is the time when folks should begin screening.
 

Q: What are the medical-legal issues for a physician who is trying to follow guideline-based care when there are different guidelines?

A: Any physician can say, “We follow the guidelines of this particular organization.” I don’t think anyone can say that an organization’s guidelines are malpractice. For individual physicians, following a set of office-based guidelines will hopefully keep them out of legal difficulty.

Q: What are the risks of overscreening, especially in breast cancer where false positives may result in invasive testing?

A: What people think of as overscreening takes a number of different forms. What one guideline would imply is overscreening is recommended screening by another guideline. I think we would all agree that in an average-risk population, beginning screening before it is recommended would be overscreening, and continuing screening when a patient has life-limiting comorbidities would constitute overscreening. Screening too frequently can constitute overscreening.

For example, many women report that their doctors still are advising a baseline mammogram at age 35. Most guideline-developing organizations would regard this as overscreening in an average-risk population.

I think we are also getting better, certainly in prostate cancer, about knowing who needs to be treated and not treated. There are a lot of cancers that would have been treated 20-30 years ago but now are being safely followed with PSA and MRI. We may be able to get to that point with breast cancer over time, too.
 

Q: Are you saying that there may be breast cancers for which active surveillance is appropriate? Is that already the case?

A: We’re not there yet. I think some of the DCIS breast cancers are part of the discussion on whether hormonal treatment or surgeries are done. I think people do have those discussions in the context of morbidity and life expectancy. Over time, we’re likely to have more cancers for which we won’t need surgical treatments.
 

Q: Why did the American Cancer Society change the upper limit for lung cancer screening from 75 to 80 years of age?

 A: For an individual older than 65, screening will now continue until the patient is 80, assuming the patient is in good health. According to the previous guideline, if a patient was 65 and more than 15 years beyond smoking cessation, then screening would end. This is exactly the time when we see lung cancers increase in the population and so a curable lung cancer would not previously have been detected by a screening CT scan. *  

Q: What role do the multicancer blood and DNA tests play in screening now?

A: As you know, the Exact Sciences Cologuard test is already included in major guidelines for colorectal cancer screening and covered by insurance. Our philosophy on multicancer early detection tests is that we’re supportive of Medicare reimbursement when two things occur: 1. When we know there’s clinical benefit, and 2. When the test has been approved by the FDA.

The multicancer early detection tests in development and undergoing prospective research would not now replace screening for the cancers with established screening programs, but if they are shown to have clinical utility for the cancers in their panel, we would be able to reduce deaths from cancers that mostly are diagnosed at late stages and have poor prognoses.

There’s going to be a need for expertise in primary care practices to help interpret the tests. These are new questions, which are well beyond what even the typical oncologist is trained in, much less primary care physicians. We and other organizations are working on providing those answers.
 

Q: While we’re on the subject of the future, how do you envision AI helping or hindering cancer screening specifically in primary care?

A: I think AI is going to help things for a couple of reasons. The ability of AI is to get through data quickly and get you information that’s personalized and useful. If AI tools could let a patient know their individual risk of a cancer in the near and long term, that would help the primary care doctor screen in an individualized way. I think AI is going to be able to improve both diagnostic radiology and pathology, and could make a very big difference in settings outside of large cancer centers that operate at high volume every day. The data look very promising for AI to contribute to risk estimation by operating like a second reader in imaging and pathology.
 

Q: Anything else you’d like to say on this subject that clinicians should know?

A: The questions about whether or not patients should be screened is being pushed on family practice doctors and internists and these questions require a relationship with the patient. A hard stopping point at age 70 when lots of people will live 20 years or more doesn’t make sense.

There’s very little data from randomized clinical trials of screening people over the age of 70. We know that cancer risk does obviously increase with age, particularly prostate and breast cancer. And these are the cancers that are going to be the most common in your practices. If someone has a known mutation, I think you’re going to look differently at screening them. And first-degree family members, particularly for the more aggressive cancers, should be considered for screening.

My philosophy on cancer screening in the elderly is that I think the guidelines are guidelines. If patients have very limited life expectancy, then they shouldn’t be screened. There are calculators that estimate life expectancy in the context of current age and current health status, and these can be useful for decision making and counseling. Patients never think their life expectancy is shorter than 10 years. If their life expectancy is longer than 10 years, then I think, all things being equal, they should continue screening, but the question of ongoing screening needs to be periodically revisited.

*This story was updated on Nov. 1, 2023.
 

The investigational anti-body drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) was associated with both improved progression-free survival and better safety than standard chemotherapy for patients with metastatic HER-2 negative (HR+/HER2–) breast cancer resistant to endocrine therapy, data from the phase 3 TROPION-Breast01 trial showed.

At a median follow-up of 10.8 months, the median progression-free survival (PFS) was 6.9 months for patients randomly assigned to receive Dato-DXd, compared with 4.9 months for the investigator’s choice of chemotherapy with either eribulin mesylate, vinorelbine, capecitabine, or gemcitabine. This difference translated into a 37% reduction in risk of disease progression with the ADC, reported Aditya Bardia, MD, MPH, director of the breast cancer research program at the Mass General Cancer Center in Boston.

Patients who received Dato-DXd had less than half the number of grade 3 or greater toxicities and fewer dose reductions or interruptions than patients who received chemotherapy, he noted in an oral abstract session at the 2023 European Society for Medical Oncology Congress.

“Overall, results support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor–positive breast cancer,” he said.
 

Different ADC, same target

Dr. Bardia noted that there is an unmet need for effective therapies for patients with metastatic HR+/HER2– breast cancer who experience disease progression after endocrine therapy and at least one line of systemic therapy.

Although chemotherapy is widely used in this population, it’s associated with low response rates, poor prognosis, and significant toxicities, including hematologic and neurologic adverse events (AEs).

Dato-DXd is composed of a monoclonal antibody targeting TROP2, a transmembrane glycoprotein overexpressed in cancer cells, linked to the topoisomerase 1 inhibitor deruxtecan as the toxic payload.

Dr. Bardia explained that Dato-DXd has four properties that distinguish it from other TROP2-directed ADCs: an optimized drug to antibody ratio of 4, a stable linker-payload, tumor-selective cleavable linker, both of which reduce off-target toxicities, and a bystander antitumor effect that can target TROP2-expressing cells in the tumor microenvironment.

In the phase I TROPION-PanTumor01 trial, Dato-DXd had promising anti-tumor activity and a manageable safety profile in patients with metastatic HR+/HER2– breast cancer, paving the way for the TROPION-Breast01 study reported here.
 

Efficacy results

In the Breast01 trial, 732 patients with inoperable or metastatic HR+/HER2– breast cancer previously treated with 1 or 2 lines of chemotherapy that had progressed on endocrine therapy were stratified by number of prior chemotherapy lines, geographic region, and prior CDK4/6 inhibitor status, and then randomized to either Dato-DXd 6 mg/kg intravenously on day 1 of each 3-week cycle (365 patients) or to investigator’s choice of chemotherapy (367 patients). According to the protocol, chemotherapy could be eribulin mesylate, vinorelbine, or gemcitabine delivered via IV on days 1 and 8 every 3 weeks, or oral capecitabine on days 1 through 14 of every 3-week cycle.

At the time of data cutoff, 93 patients assigned to the ADC and 39 assigned to chemotherapy were still on treatment.

As noted before, median PFS by blinded independent central review, one of two primary endpoints, was 6.9 months with Dato-DXd, compared with 4.9 months with chemotherapy, translating into a hazard ratio for progression of 0.63 (P < .0001)­­­.

The benefit was seen across nearly all subgroups except among patients who had not previously received a CDK4/6 inhibitor, and patients who had received a prior anthracycline but not a taxane.­

Objective response rates (ORR) were 36.4% with Dato-DXd (99.5% partial and .5% complete response), compared with 22.9% with chemotherapy (all partial responses; P values not reported).

Overall survival data, the other primary endpoint, were not mature at a median OS follow-up of 9.7 months, and will be reported at a later date.
 

­Safety results

“In terms of safety, the rate of grade 3 or higher treatment-related AEs in the Dato-DXd arm was less as compared to investigator choice of chemotherapy. This is a bit different from most of the studies; in general we see that the rate of adverse events is higher in the intervention arm as compared to the control arm,” Dr. Bardia commented.

Rates of dose reductions and dose interruptions due to treatment-related AEs were also lower with the ADC.

There were no patient deaths associated with Dato-DXd. One patient assigned to chemotherapy died from a complication associated with febrile neutropenia.

Most treatment-related AEs occurring in 15% of patients and AEs of special interest were of grade 1 and manageable.

The most common toxicities seen with the ADC were oral mucositis and dry eye. The most common side effects with chemotherapy were neutropenia and anemia, “the usual side effects you would expect with chemotherapy,” Dr. Bardia said, pointing out that the rate of grade 3 neutropenia was 31% with standard chemotherapy, compared with 1% with Dato-DXd.
 

Good, but we can do better

ESMO invited discussant Sarat Chandarlapaty, MD, PhD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York, commented that while the trial data showed superior efficacy and safety with Dato-DXd, compared with standard chemotherapy, it’s still unclear how it and other ADCs on the market and in the research pipeline may be used in therapy for this patient population.

“Would I rather prescribe Dato-DXd or more chemo after 1 to 2 lines of chemo in unselected HR-positive, HER2-negative breast cancer? The answer is Dato-DXd, but it leaves several unanswered questions for us,” he said.

“First, we have two ADCs approved in HR-positive breast cancer: another TROP2 ADC sacituzumab [govitecan] and a HER2 ADC trastuzumab deruxtecan. Would I rather give Dato over one of these? I don’t have an answer,” he added.

In addition, it’s unknown whether these drugs, which have the same topoisomerase-targeted payload, could be given in sequence, and there are as yet no clear answers as to whether patients might do better with Dato-DXd or with a PIK3ca inhibitor.

“I would say that the elephant in the room is really another question, and that is, ‘Is Dato-DXd in this context delivering on the promise of an ADC?’ ” Dr. Chandarlapaty said.

“I think translational research is urgently needed if we’re ultimately to deliver on the promise of these agents in the clinic,” he concluded.

The TROPION-Breast01 study is sponsored AstraZeneca, which is collaborating with Daiichi-Sankyo on global development and commercialization of Dato-DXd. Dr. Bardia disclosed advisory board activities and institutional research funding from AstraZeneca and Daiichi-Sankyo and others. Dr. Chandarlapaty disclosed research funding from both companies, and advisory board activities for AstraZeneca and others.

The investigational anti-body drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) was associated with both improved progression-free survival and better safety than standard chemotherapy for patients with metastatic HER-2 negative (HR+/HER2–) breast cancer resistant to endocrine therapy, data from the phase 3 TROPION-Breast01 trial showed.

At a median follow-up of 10.8 months, the median progression-free survival (PFS) was 6.9 months for patients randomly assigned to receive Dato-DXd, compared with 4.9 months for the investigator’s choice of chemotherapy with either eribulin mesylate, vinorelbine, capecitabine, or gemcitabine. This difference translated into a 37% reduction in risk of disease progression with the ADC, reported Aditya Bardia, MD, MPH, director of the breast cancer research program at the Mass General Cancer Center in Boston.

Patients who received Dato-DXd had less than half the number of grade 3 or greater toxicities and fewer dose reductions or interruptions than patients who received chemotherapy, he noted in an oral abstract session at the 2023 European Society for Medical Oncology Congress.

“Overall, results support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor–positive breast cancer,” he said.
 

Different ADC, same target

Dr. Bardia noted that there is an unmet need for effective therapies for patients with metastatic HR+/HER2– breast cancer who experience disease progression after endocrine therapy and at least one line of systemic therapy.

Although chemotherapy is widely used in this population, it’s associated with low response rates, poor prognosis, and significant toxicities, including hematologic and neurologic adverse events (AEs).

Dato-DXd is composed of a monoclonal antibody targeting TROP2, a transmembrane glycoprotein overexpressed in cancer cells, linked to the topoisomerase 1 inhibitor deruxtecan as the toxic payload.

Dr. Bardia explained that Dato-DXd has four properties that distinguish it from other TROP2-directed ADCs: an optimized drug to antibody ratio of 4, a stable linker-payload, tumor-selective cleavable linker, both of which reduce off-target toxicities, and a bystander antitumor effect that can target TROP2-expressing cells in the tumor microenvironment.

In the phase I TROPION-PanTumor01 trial, Dato-DXd had promising anti-tumor activity and a manageable safety profile in patients with metastatic HR+/HER2– breast cancer, paving the way for the TROPION-Breast01 study reported here.
 

Efficacy results

In the Breast01 trial, 732 patients with inoperable or metastatic HR+/HER2– breast cancer previously treated with 1 or 2 lines of chemotherapy that had progressed on endocrine therapy were stratified by number of prior chemotherapy lines, geographic region, and prior CDK4/6 inhibitor status, and then randomized to either Dato-DXd 6 mg/kg intravenously on day 1 of each 3-week cycle (365 patients) or to investigator’s choice of chemotherapy (367 patients). According to the protocol, chemotherapy could be eribulin mesylate, vinorelbine, or gemcitabine delivered via IV on days 1 and 8 every 3 weeks, or oral capecitabine on days 1 through 14 of every 3-week cycle.

At the time of data cutoff, 93 patients assigned to the ADC and 39 assigned to chemotherapy were still on treatment.

As noted before, median PFS by blinded independent central review, one of two primary endpoints, was 6.9 months with Dato-DXd, compared with 4.9 months with chemotherapy, translating into a hazard ratio for progression of 0.63 (P < .0001)­­­.

The benefit was seen across nearly all subgroups except among patients who had not previously received a CDK4/6 inhibitor, and patients who had received a prior anthracycline but not a taxane.­

Objective response rates (ORR) were 36.4% with Dato-DXd (99.5% partial and .5% complete response), compared with 22.9% with chemotherapy (all partial responses; P values not reported).

Overall survival data, the other primary endpoint, were not mature at a median OS follow-up of 9.7 months, and will be reported at a later date.
 

­Safety results

“In terms of safety, the rate of grade 3 or higher treatment-related AEs in the Dato-DXd arm was less as compared to investigator choice of chemotherapy. This is a bit different from most of the studies; in general we see that the rate of adverse events is higher in the intervention arm as compared to the control arm,” Dr. Bardia commented.

Rates of dose reductions and dose interruptions due to treatment-related AEs were also lower with the ADC.

There were no patient deaths associated with Dato-DXd. One patient assigned to chemotherapy died from a complication associated with febrile neutropenia.

Most treatment-related AEs occurring in 15% of patients and AEs of special interest were of grade 1 and manageable.

The most common toxicities seen with the ADC were oral mucositis and dry eye. The most common side effects with chemotherapy were neutropenia and anemia, “the usual side effects you would expect with chemotherapy,” Dr. Bardia said, pointing out that the rate of grade 3 neutropenia was 31% with standard chemotherapy, compared with 1% with Dato-DXd.
 

Good, but we can do better

ESMO invited discussant Sarat Chandarlapaty, MD, PhD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York, commented that while the trial data showed superior efficacy and safety with Dato-DXd, compared with standard chemotherapy, it’s still unclear how it and other ADCs on the market and in the research pipeline may be used in therapy for this patient population.

“Would I rather prescribe Dato-DXd or more chemo after 1 to 2 lines of chemo in unselected HR-positive, HER2-negative breast cancer? The answer is Dato-DXd, but it leaves several unanswered questions for us,” he said.

“First, we have two ADCs approved in HR-positive breast cancer: another TROP2 ADC sacituzumab [govitecan] and a HER2 ADC trastuzumab deruxtecan. Would I rather give Dato over one of these? I don’t have an answer,” he added.

In addition, it’s unknown whether these drugs, which have the same topoisomerase-targeted payload, could be given in sequence, and there are as yet no clear answers as to whether patients might do better with Dato-DXd or with a PIK3ca inhibitor.

“I would say that the elephant in the room is really another question, and that is, ‘Is Dato-DXd in this context delivering on the promise of an ADC?’ ” Dr. Chandarlapaty said.

“I think translational research is urgently needed if we’re ultimately to deliver on the promise of these agents in the clinic,” he concluded.

The TROPION-Breast01 study is sponsored AstraZeneca, which is collaborating with Daiichi-Sankyo on global development and commercialization of Dato-DXd. Dr. Bardia disclosed advisory board activities and institutional research funding from AstraZeneca and Daiichi-Sankyo and others. Dr. Chandarlapaty disclosed research funding from both companies, and advisory board activities for AstraZeneca and others.

The investigational anti-body drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) was associated with both improved progression-free survival and better safety than standard chemotherapy for patients with metastatic HER-2 negative (HR+/HER2–) breast cancer resistant to endocrine therapy, data from the phase 3 TROPION-Breast01 trial showed.

At a median follow-up of 10.8 months, the median progression-free survival (PFS) was 6.9 months for patients randomly assigned to receive Dato-DXd, compared with 4.9 months for the investigator’s choice of chemotherapy with either eribulin mesylate, vinorelbine, capecitabine, or gemcitabine. This difference translated into a 37% reduction in risk of disease progression with the ADC, reported Aditya Bardia, MD, MPH, director of the breast cancer research program at the Mass General Cancer Center in Boston.

Patients who received Dato-DXd had less than half the number of grade 3 or greater toxicities and fewer dose reductions or interruptions than patients who received chemotherapy, he noted in an oral abstract session at the 2023 European Society for Medical Oncology Congress.

“Overall, results support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor–positive breast cancer,” he said.
 

Different ADC, same target

Dr. Bardia noted that there is an unmet need for effective therapies for patients with metastatic HR+/HER2– breast cancer who experience disease progression after endocrine therapy and at least one line of systemic therapy.

Although chemotherapy is widely used in this population, it’s associated with low response rates, poor prognosis, and significant toxicities, including hematologic and neurologic adverse events (AEs).

Dato-DXd is composed of a monoclonal antibody targeting TROP2, a transmembrane glycoprotein overexpressed in cancer cells, linked to the topoisomerase 1 inhibitor deruxtecan as the toxic payload.

Dr. Bardia explained that Dato-DXd has four properties that distinguish it from other TROP2-directed ADCs: an optimized drug to antibody ratio of 4, a stable linker-payload, tumor-selective cleavable linker, both of which reduce off-target toxicities, and a bystander antitumor effect that can target TROP2-expressing cells in the tumor microenvironment.

In the phase I TROPION-PanTumor01 trial, Dato-DXd had promising anti-tumor activity and a manageable safety profile in patients with metastatic HR+/HER2– breast cancer, paving the way for the TROPION-Breast01 study reported here.
 

Efficacy results

In the Breast01 trial, 732 patients with inoperable or metastatic HR+/HER2– breast cancer previously treated with 1 or 2 lines of chemotherapy that had progressed on endocrine therapy were stratified by number of prior chemotherapy lines, geographic region, and prior CDK4/6 inhibitor status, and then randomized to either Dato-DXd 6 mg/kg intravenously on day 1 of each 3-week cycle (365 patients) or to investigator’s choice of chemotherapy (367 patients). According to the protocol, chemotherapy could be eribulin mesylate, vinorelbine, or gemcitabine delivered via IV on days 1 and 8 every 3 weeks, or oral capecitabine on days 1 through 14 of every 3-week cycle.

At the time of data cutoff, 93 patients assigned to the ADC and 39 assigned to chemotherapy were still on treatment.

As noted before, median PFS by blinded independent central review, one of two primary endpoints, was 6.9 months with Dato-DXd, compared with 4.9 months with chemotherapy, translating into a hazard ratio for progression of 0.63 (P < .0001)­­­.

The benefit was seen across nearly all subgroups except among patients who had not previously received a CDK4/6 inhibitor, and patients who had received a prior anthracycline but not a taxane.­

Objective response rates (ORR) were 36.4% with Dato-DXd (99.5% partial and .5% complete response), compared with 22.9% with chemotherapy (all partial responses; P values not reported).

Overall survival data, the other primary endpoint, were not mature at a median OS follow-up of 9.7 months, and will be reported at a later date.
 

­Safety results

“In terms of safety, the rate of grade 3 or higher treatment-related AEs in the Dato-DXd arm was less as compared to investigator choice of chemotherapy. This is a bit different from most of the studies; in general we see that the rate of adverse events is higher in the intervention arm as compared to the control arm,” Dr. Bardia commented.

Rates of dose reductions and dose interruptions due to treatment-related AEs were also lower with the ADC.

There were no patient deaths associated with Dato-DXd. One patient assigned to chemotherapy died from a complication associated with febrile neutropenia.

Most treatment-related AEs occurring in 15% of patients and AEs of special interest were of grade 1 and manageable.

The most common toxicities seen with the ADC were oral mucositis and dry eye. The most common side effects with chemotherapy were neutropenia and anemia, “the usual side effects you would expect with chemotherapy,” Dr. Bardia said, pointing out that the rate of grade 3 neutropenia was 31% with standard chemotherapy, compared with 1% with Dato-DXd.
 

Good, but we can do better

ESMO invited discussant Sarat Chandarlapaty, MD, PhD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York, commented that while the trial data showed superior efficacy and safety with Dato-DXd, compared with standard chemotherapy, it’s still unclear how it and other ADCs on the market and in the research pipeline may be used in therapy for this patient population.

“Would I rather prescribe Dato-DXd or more chemo after 1 to 2 lines of chemo in unselected HR-positive, HER2-negative breast cancer? The answer is Dato-DXd, but it leaves several unanswered questions for us,” he said.

“First, we have two ADCs approved in HR-positive breast cancer: another TROP2 ADC sacituzumab [govitecan] and a HER2 ADC trastuzumab deruxtecan. Would I rather give Dato over one of these? I don’t have an answer,” he added.

In addition, it’s unknown whether these drugs, which have the same topoisomerase-targeted payload, could be given in sequence, and there are as yet no clear answers as to whether patients might do better with Dato-DXd or with a PIK3ca inhibitor.

“I would say that the elephant in the room is really another question, and that is, ‘Is Dato-DXd in this context delivering on the promise of an ADC?’ ” Dr. Chandarlapaty said.

“I think translational research is urgently needed if we’re ultimately to deliver on the promise of these agents in the clinic,” he concluded.

The TROPION-Breast01 study is sponsored AstraZeneca, which is collaborating with Daiichi-Sankyo on global development and commercialization of Dato-DXd. Dr. Bardia disclosed advisory board activities and institutional research funding from AstraZeneca and Daiichi-Sankyo and others. Dr. Chandarlapaty disclosed research funding from both companies, and advisory board activities for AstraZeneca and others.

MADRID – “Why did I choose this?”

That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.

“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.

This oncologist is hardly alone.

Rates of burnout among oncologists remain alarmingly high, explained session chair Kok Haw Jonathan Lim, MD, PhD.

A survey from ESMO conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.

This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.

More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.

Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.

The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.

Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.

Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.

Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.

“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.

While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.

In response to this chronic and growing problem, ESMO launched its Resilience Task Force in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.

A panel of experts at the meeting touched on some of these solutions.

Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.

Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.

“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”

The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.

However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”

But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”

In other words, oncologists need to be able to set boundaries and say no.

Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.

Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.

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

MADRID – “Why did I choose this?”

That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.

“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.

This oncologist is hardly alone.

Rates of burnout among oncologists remain alarmingly high, explained session chair Kok Haw Jonathan Lim, MD, PhD.

A survey from ESMO conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.

This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.

More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.

Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.

The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.

Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.

Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.

Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.

“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.

While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.

In response to this chronic and growing problem, ESMO launched its Resilience Task Force in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.

A panel of experts at the meeting touched on some of these solutions.

Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.

Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.

“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”

The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.

However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”

But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”

In other words, oncologists need to be able to set boundaries and say no.

Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.

Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.

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

MADRID – “Why did I choose this?”

That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.

“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.

This oncologist is hardly alone.

Rates of burnout among oncologists remain alarmingly high, explained session chair Kok Haw Jonathan Lim, MD, PhD.

A survey from ESMO conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.

This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.

More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.

Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.

The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.

Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.

Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.

Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.

“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.

While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.

In response to this chronic and growing problem, ESMO launched its Resilience Task Force in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.

A panel of experts at the meeting touched on some of these solutions.

Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.

Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.

“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”

The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.

However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”

But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”

In other words, oncologists need to be able to set boundaries and say no.

Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.

Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.

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

The U.S. Food and Drug Administration has approved tablets of ivosidenib (Tibsovo, Servier Pharmaceuticals) for adults with isocitrate dehydrogenase (IDH)-1 mutated relapsed or refractory myelodysplastic syndromes.

The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.

Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.

Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.

The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.

Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.

Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.

Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.

Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.

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

The U.S. Food and Drug Administration has approved tablets of ivosidenib (Tibsovo, Servier Pharmaceuticals) for adults with isocitrate dehydrogenase (IDH)-1 mutated relapsed or refractory myelodysplastic syndromes.

The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.

Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.

Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.

The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.

Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.

Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.

Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.

Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.

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

The U.S. Food and Drug Administration has approved tablets of ivosidenib (Tibsovo, Servier Pharmaceuticals) for adults with isocitrate dehydrogenase (IDH)-1 mutated relapsed or refractory myelodysplastic syndromes.

The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.

Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.

Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.

The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.

Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.

Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.

Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.

Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.

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

Enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) is being called the new standard of care for the upfront treatment of locally advanced/metastatic urothelial carcinoma following a phase 3 trial presented at the 2023 European Society for Medical Oncology annual meeting.

The combination soundly beat the current standard of care – platinum-based chemotherapy – with a median overall survival of 31.5 months among 442 subjects versus 16.1 months among 444 randomized to gemcitabine with cisplatin or carboplatin, an unprecedented 53% drop in the risk of mortality (P < .00001).

The elimination of chemotherapy also meant that there were substantially fewer grade 3 or higher adverse events with the new combination.

“This is the first time we’ve managed to beat chemotherapy in the first-line setting for overall survival despite multiple previous attempts.” The 30% remission rate with enfortumab vedotin plus pembrolizumab “is not something we’ve seen before,” said lead investigator Thomas Powles, MBBS, MD, a urologic oncologist and researcher at the University of London, who presented the findings.

“We welcome a new standard of care in the management of advanced, metastatic urothelial carcinoma, enfortumab vedotin plus pembrolizumab,” said Andrea Apolo, MD, a urologic oncology researcher at the National Cancer Institute in Bethesda, Md., and discussant on the trial, dubbed EV-302/KEYNOTE-A39.

The news overshadowed a second trial presented immediately after Dr. Powles’ that also showed improvement in overall survival versus standard platinum-based chemotherapy, CheckMate 901.

Instead of replacing chemotherapy, CheckMate 901 added nivolumab. With 304 patients randomized to each arm, nivolumab add-on led to a median overall survival of 21.7 months versus 18.9 months with stand-alone gemcitabine/cisplatin, a 22% drop in the risk of mortality (P = .0171).

It’s the first time that adding immunotherapy to first-line chemotherapy improved survival in metastatic urothelial carcinoma, said lead investigator Michiel van der Heijden, MD, PhD, a urologic oncologist and researcher at the Netherlands Cancer Institute, Amsterdam.

After decades of stagnation, Dr. Apolo said, it’s “monumental for our field” to have two trials that beat chemotherapy in the first-line setting.

However, she said that the much better survival with enfortumab vedotin/pembrolizumab means that the combination now “takes first place as the best first-line regimen in urothelial carcinoma.”
 

Major disruptions in the treatment paradigm

The crowning of a new first-line standard for locally advanced/metastatic urothelial carcinoma means that everything else in the treatment paradigm has to shift, Dr. Apolo said, and there are many new questions that need to be answered.

Among the most pressing, should the previous first-line standard – platinum-based chemotherapy – now move to the second line and be considered the treatment of choice after progression? Also, is there still a role for the previous second-line standards, pembrolizumab and other immunotherapies, if pembrolizumab fails in the first line?

Dr. Apolo said investigators also need to figure out if there is a role for enfortumab vedotin/pembrolizumab in earlier-stage disease, such as muscle-invasive bladder cancer, and if the dose and duration of enfortumab vedotin can be reduced to limit its peculiar ocular and other toxicities.

Finally, “we must discuss cost,” she said. Enfortumab vedotin plus pembrolizumab (EV+P) is expensive. “Will payers be able to afford” it?

Dr. Powles, the lead investigator on EV-302/KEYNOTE-A39, said he doesn’t know how negotiations are going with payers, but that he hopes they move quickly. “We’ve seen transformative results” with the combination for even aggressive cancers in very sick people. “I think it’s going to be a challenge with patients not to talk about these data.”
 

EV-302/KEYNOTE-059 details

Merck, the maker of pembrolizumab, and the makers/marketers of enfortumab vedotin, Astellas and Seagen, said they will use EV-302/KEYNOTE-059 to seek a first-line indication for locally advanced/metastatic urothelial carcinoma from the U.S. Food and Drug Administration and other regulators.

They also said the results serve as the confirmation FDA required when it gave accelerated approval to the combination in April 2023 for cisplatin-ineligible patients based on tumor response rates and response durability, according to press releases from the companies.

Pembrolizumab (P) in the trial was dosed at 200 mg on the first day of 3-week treatment cycles to a maximum of 35 cycles; enfortumab vedotin (EV) was given on the first and eighth day of the cycle with no limit in the number of cycles until progression or unacceptable toxicity.

Cisplatin or carboplatin (C) in the control arm was delivered on the first day and gemcitabine (G) on the first and eighth days for up to six 3-week cycles.

Patients in both arms were split about equally between performance statuses of 0 or 1; less than 4% in each group had statuses of 2.

Echoing the overall survival (OS) results, progression-free survival (PFS) was a median of 12.5 months with EV-P versus 6.3 months with GC, a 55% drop in the risk of progression or death (P < .00001).

The results held regardless of PD-L1 expression, cisplatin eligibility, and the presence or absence of visceral metastases.

Follow-up treatments in the trial begin to address Dr. Apolo’s questions: Almost 60% of GC patients went on to a PD-1/L1 for subsequent maintenance or progression, and almost a quarter of EV+P patients went on to subsequent platinum-based chemotherapy.

Grade 3 or higher adverse events occurred in 55.9% of subjects in the EV+P group versus 69.5% in the GC arm.

The most common in the chemotherapy arm were anemia, neutropenia, thrombocytopenia, fatigue, and nausea. The most common with EV+P were skin reactions, hyperglycemia, neutropenia, peripheral neuropathy, diarrhea, and anemia,
 

CheckMate 901 details

In CheckMate 901, gemcitabine and cisplatin were administered on the first day of 3-week treatment cycles for up to 6 cycles; subjects randomized to nivolumab add-on received 360 mg on day 1 of each cycle, followed by 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 2 years.

PFS results again mirrored OS, with a median PFS of 7.9 months in the nivolumab arm versus 7.6 months with stand-alone chemotherapy, a 28% drop in the risk of progression or death (P = .0012).

Although OS and PFS benefits were statistically significant overall, they were not significant in subgroup analyses of patients 65 years and older, women, or in patients with liver metastases.

Trends in OS and PFS actually favored chemotherapy in the 40 U.S. subjects (HR OS, 1.92; 95% confidence interval, 0.95-3.88).

The rate of grade 3 or higher adverse events was 61.8% with nivolumab add-on versus 51.7% with chemotherapy alone. Anemia and neutropenia were the most common in both arms, and higher in the nivolumab group.

EV-302/KEYNOTE-A39 was funded by Seagen, Astellas, and Merck. CheckMate 901 was funded by Bristol-Myers Squibb, the maker of nivolumab.

Dr. Powles reported extensive financial ties to pharmaceutical companies, including being an advisor to and receiving research funding from Bristol-Myers Squibb, Merck, SeaGen, and Astellas, as well as travel expenses from Merck. Among other disclosures, Dr. Heijden is an advisor to Seagen and an advisor and researcher for Bristol-Myers Squibb. Dr. Apolo is an unpaid consultant to Merck, Astellas, Seagen, Bristol-Myers Squibb, and other companies.

Enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) is being called the new standard of care for the upfront treatment of locally advanced/metastatic urothelial carcinoma following a phase 3 trial presented at the 2023 European Society for Medical Oncology annual meeting.

The combination soundly beat the current standard of care – platinum-based chemotherapy – with a median overall survival of 31.5 months among 442 subjects versus 16.1 months among 444 randomized to gemcitabine with cisplatin or carboplatin, an unprecedented 53% drop in the risk of mortality (P < .00001).

The elimination of chemotherapy also meant that there were substantially fewer grade 3 or higher adverse events with the new combination.

“This is the first time we’ve managed to beat chemotherapy in the first-line setting for overall survival despite multiple previous attempts.” The 30% remission rate with enfortumab vedotin plus pembrolizumab “is not something we’ve seen before,” said lead investigator Thomas Powles, MBBS, MD, a urologic oncologist and researcher at the University of London, who presented the findings.

“We welcome a new standard of care in the management of advanced, metastatic urothelial carcinoma, enfortumab vedotin plus pembrolizumab,” said Andrea Apolo, MD, a urologic oncology researcher at the National Cancer Institute in Bethesda, Md., and discussant on the trial, dubbed EV-302/KEYNOTE-A39.

The news overshadowed a second trial presented immediately after Dr. Powles’ that also showed improvement in overall survival versus standard platinum-based chemotherapy, CheckMate 901.

Instead of replacing chemotherapy, CheckMate 901 added nivolumab. With 304 patients randomized to each arm, nivolumab add-on led to a median overall survival of 21.7 months versus 18.9 months with stand-alone gemcitabine/cisplatin, a 22% drop in the risk of mortality (P = .0171).

It’s the first time that adding immunotherapy to first-line chemotherapy improved survival in metastatic urothelial carcinoma, said lead investigator Michiel van der Heijden, MD, PhD, a urologic oncologist and researcher at the Netherlands Cancer Institute, Amsterdam.

After decades of stagnation, Dr. Apolo said, it’s “monumental for our field” to have two trials that beat chemotherapy in the first-line setting.

However, she said that the much better survival with enfortumab vedotin/pembrolizumab means that the combination now “takes first place as the best first-line regimen in urothelial carcinoma.”
 

Major disruptions in the treatment paradigm

The crowning of a new first-line standard for locally advanced/metastatic urothelial carcinoma means that everything else in the treatment paradigm has to shift, Dr. Apolo said, and there are many new questions that need to be answered.

Among the most pressing, should the previous first-line standard – platinum-based chemotherapy – now move to the second line and be considered the treatment of choice after progression? Also, is there still a role for the previous second-line standards, pembrolizumab and other immunotherapies, if pembrolizumab fails in the first line?

Dr. Apolo said investigators also need to figure out if there is a role for enfortumab vedotin/pembrolizumab in earlier-stage disease, such as muscle-invasive bladder cancer, and if the dose and duration of enfortumab vedotin can be reduced to limit its peculiar ocular and other toxicities.

Finally, “we must discuss cost,” she said. Enfortumab vedotin plus pembrolizumab (EV+P) is expensive. “Will payers be able to afford” it?

Dr. Powles, the lead investigator on EV-302/KEYNOTE-A39, said he doesn’t know how negotiations are going with payers, but that he hopes they move quickly. “We’ve seen transformative results” with the combination for even aggressive cancers in very sick people. “I think it’s going to be a challenge with patients not to talk about these data.”
 

EV-302/KEYNOTE-059 details

Merck, the maker of pembrolizumab, and the makers/marketers of enfortumab vedotin, Astellas and Seagen, said they will use EV-302/KEYNOTE-059 to seek a first-line indication for locally advanced/metastatic urothelial carcinoma from the U.S. Food and Drug Administration and other regulators.

They also said the results serve as the confirmation FDA required when it gave accelerated approval to the combination in April 2023 for cisplatin-ineligible patients based on tumor response rates and response durability, according to press releases from the companies.

Pembrolizumab (P) in the trial was dosed at 200 mg on the first day of 3-week treatment cycles to a maximum of 35 cycles; enfortumab vedotin (EV) was given on the first and eighth day of the cycle with no limit in the number of cycles until progression or unacceptable toxicity.

Cisplatin or carboplatin (C) in the control arm was delivered on the first day and gemcitabine (G) on the first and eighth days for up to six 3-week cycles.

Patients in both arms were split about equally between performance statuses of 0 or 1; less than 4% in each group had statuses of 2.

Echoing the overall survival (OS) results, progression-free survival (PFS) was a median of 12.5 months with EV-P versus 6.3 months with GC, a 55% drop in the risk of progression or death (P < .00001).

The results held regardless of PD-L1 expression, cisplatin eligibility, and the presence or absence of visceral metastases.

Follow-up treatments in the trial begin to address Dr. Apolo’s questions: Almost 60% of GC patients went on to a PD-1/L1 for subsequent maintenance or progression, and almost a quarter of EV+P patients went on to subsequent platinum-based chemotherapy.

Grade 3 or higher adverse events occurred in 55.9% of subjects in the EV+P group versus 69.5% in the GC arm.

The most common in the chemotherapy arm were anemia, neutropenia, thrombocytopenia, fatigue, and nausea. The most common with EV+P were skin reactions, hyperglycemia, neutropenia, peripheral neuropathy, diarrhea, and anemia,
 

CheckMate 901 details

In CheckMate 901, gemcitabine and cisplatin were administered on the first day of 3-week treatment cycles for up to 6 cycles; subjects randomized to nivolumab add-on received 360 mg on day 1 of each cycle, followed by 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 2 years.

PFS results again mirrored OS, with a median PFS of 7.9 months in the nivolumab arm versus 7.6 months with stand-alone chemotherapy, a 28% drop in the risk of progression or death (P = .0012).

Although OS and PFS benefits were statistically significant overall, they were not significant in subgroup analyses of patients 65 years and older, women, or in patients with liver metastases.

Trends in OS and PFS actually favored chemotherapy in the 40 U.S. subjects (HR OS, 1.92; 95% confidence interval, 0.95-3.88).

The rate of grade 3 or higher adverse events was 61.8% with nivolumab add-on versus 51.7% with chemotherapy alone. Anemia and neutropenia were the most common in both arms, and higher in the nivolumab group.

EV-302/KEYNOTE-A39 was funded by Seagen, Astellas, and Merck. CheckMate 901 was funded by Bristol-Myers Squibb, the maker of nivolumab.

Dr. Powles reported extensive financial ties to pharmaceutical companies, including being an advisor to and receiving research funding from Bristol-Myers Squibb, Merck, SeaGen, and Astellas, as well as travel expenses from Merck. Among other disclosures, Dr. Heijden is an advisor to Seagen and an advisor and researcher for Bristol-Myers Squibb. Dr. Apolo is an unpaid consultant to Merck, Astellas, Seagen, Bristol-Myers Squibb, and other companies.

Enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) is being called the new standard of care for the upfront treatment of locally advanced/metastatic urothelial carcinoma following a phase 3 trial presented at the 2023 European Society for Medical Oncology annual meeting.

The combination soundly beat the current standard of care – platinum-based chemotherapy – with a median overall survival of 31.5 months among 442 subjects versus 16.1 months among 444 randomized to gemcitabine with cisplatin or carboplatin, an unprecedented 53% drop in the risk of mortality (P < .00001).

The elimination of chemotherapy also meant that there were substantially fewer grade 3 or higher adverse events with the new combination.

“This is the first time we’ve managed to beat chemotherapy in the first-line setting for overall survival despite multiple previous attempts.” The 30% remission rate with enfortumab vedotin plus pembrolizumab “is not something we’ve seen before,” said lead investigator Thomas Powles, MBBS, MD, a urologic oncologist and researcher at the University of London, who presented the findings.

“We welcome a new standard of care in the management of advanced, metastatic urothelial carcinoma, enfortumab vedotin plus pembrolizumab,” said Andrea Apolo, MD, a urologic oncology researcher at the National Cancer Institute in Bethesda, Md., and discussant on the trial, dubbed EV-302/KEYNOTE-A39.

The news overshadowed a second trial presented immediately after Dr. Powles’ that also showed improvement in overall survival versus standard platinum-based chemotherapy, CheckMate 901.

Instead of replacing chemotherapy, CheckMate 901 added nivolumab. With 304 patients randomized to each arm, nivolumab add-on led to a median overall survival of 21.7 months versus 18.9 months with stand-alone gemcitabine/cisplatin, a 22% drop in the risk of mortality (P = .0171).

It’s the first time that adding immunotherapy to first-line chemotherapy improved survival in metastatic urothelial carcinoma, said lead investigator Michiel van der Heijden, MD, PhD, a urologic oncologist and researcher at the Netherlands Cancer Institute, Amsterdam.

After decades of stagnation, Dr. Apolo said, it’s “monumental for our field” to have two trials that beat chemotherapy in the first-line setting.

However, she said that the much better survival with enfortumab vedotin/pembrolizumab means that the combination now “takes first place as the best first-line regimen in urothelial carcinoma.”
 

Major disruptions in the treatment paradigm

The crowning of a new first-line standard for locally advanced/metastatic urothelial carcinoma means that everything else in the treatment paradigm has to shift, Dr. Apolo said, and there are many new questions that need to be answered.

Among the most pressing, should the previous first-line standard – platinum-based chemotherapy – now move to the second line and be considered the treatment of choice after progression? Also, is there still a role for the previous second-line standards, pembrolizumab and other immunotherapies, if pembrolizumab fails in the first line?

Dr. Apolo said investigators also need to figure out if there is a role for enfortumab vedotin/pembrolizumab in earlier-stage disease, such as muscle-invasive bladder cancer, and if the dose and duration of enfortumab vedotin can be reduced to limit its peculiar ocular and other toxicities.

Finally, “we must discuss cost,” she said. Enfortumab vedotin plus pembrolizumab (EV+P) is expensive. “Will payers be able to afford” it?

Dr. Powles, the lead investigator on EV-302/KEYNOTE-A39, said he doesn’t know how negotiations are going with payers, but that he hopes they move quickly. “We’ve seen transformative results” with the combination for even aggressive cancers in very sick people. “I think it’s going to be a challenge with patients not to talk about these data.”
 

EV-302/KEYNOTE-059 details

Merck, the maker of pembrolizumab, and the makers/marketers of enfortumab vedotin, Astellas and Seagen, said they will use EV-302/KEYNOTE-059 to seek a first-line indication for locally advanced/metastatic urothelial carcinoma from the U.S. Food and Drug Administration and other regulators.

They also said the results serve as the confirmation FDA required when it gave accelerated approval to the combination in April 2023 for cisplatin-ineligible patients based on tumor response rates and response durability, according to press releases from the companies.

Pembrolizumab (P) in the trial was dosed at 200 mg on the first day of 3-week treatment cycles to a maximum of 35 cycles; enfortumab vedotin (EV) was given on the first and eighth day of the cycle with no limit in the number of cycles until progression or unacceptable toxicity.

Cisplatin or carboplatin (C) in the control arm was delivered on the first day and gemcitabine (G) on the first and eighth days for up to six 3-week cycles.

Patients in both arms were split about equally between performance statuses of 0 or 1; less than 4% in each group had statuses of 2.

Echoing the overall survival (OS) results, progression-free survival (PFS) was a median of 12.5 months with EV-P versus 6.3 months with GC, a 55% drop in the risk of progression or death (P < .00001).

The results held regardless of PD-L1 expression, cisplatin eligibility, and the presence or absence of visceral metastases.

Follow-up treatments in the trial begin to address Dr. Apolo’s questions: Almost 60% of GC patients went on to a PD-1/L1 for subsequent maintenance or progression, and almost a quarter of EV+P patients went on to subsequent platinum-based chemotherapy.

Grade 3 or higher adverse events occurred in 55.9% of subjects in the EV+P group versus 69.5% in the GC arm.

The most common in the chemotherapy arm were anemia, neutropenia, thrombocytopenia, fatigue, and nausea. The most common with EV+P were skin reactions, hyperglycemia, neutropenia, peripheral neuropathy, diarrhea, and anemia,
 

CheckMate 901 details

In CheckMate 901, gemcitabine and cisplatin were administered on the first day of 3-week treatment cycles for up to 6 cycles; subjects randomized to nivolumab add-on received 360 mg on day 1 of each cycle, followed by 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 2 years.

PFS results again mirrored OS, with a median PFS of 7.9 months in the nivolumab arm versus 7.6 months with stand-alone chemotherapy, a 28% drop in the risk of progression or death (P = .0012).

Although OS and PFS benefits were statistically significant overall, they were not significant in subgroup analyses of patients 65 years and older, women, or in patients with liver metastases.

Trends in OS and PFS actually favored chemotherapy in the 40 U.S. subjects (HR OS, 1.92; 95% confidence interval, 0.95-3.88).

The rate of grade 3 or higher adverse events was 61.8% with nivolumab add-on versus 51.7% with chemotherapy alone. Anemia and neutropenia were the most common in both arms, and higher in the nivolumab group.

EV-302/KEYNOTE-A39 was funded by Seagen, Astellas, and Merck. CheckMate 901 was funded by Bristol-Myers Squibb, the maker of nivolumab.

Dr. Powles reported extensive financial ties to pharmaceutical companies, including being an advisor to and receiving research funding from Bristol-Myers Squibb, Merck, SeaGen, and Astellas, as well as travel expenses from Merck. Among other disclosures, Dr. Heijden is an advisor to Seagen and an advisor and researcher for Bristol-Myers Squibb. Dr. Apolo is an unpaid consultant to Merck, Astellas, Seagen, Bristol-Myers Squibb, and other companies.

There is an urgent need to raise global awareness about the direct link between alcohol consumption and cancer risk.

That message was delivered by Isabelle Soerjomataram, PhD, with the International Agency for Research on Cancer (IARC), Lyon, France, at a session devoted to alcohol and cancer at the annual meeting of the European Society for Medical Oncology.

“Global awareness about the link between alcohol and cancer continues to be very low,” Dr. Soerjomataram told the audience. “Health professionals – oncologists, nurses, medical doctors, GPs – have an important role in increasing awareness and bringing this knowledge to people, which may lead to reduced consumption.”

Session chair Gilberto Morgan, MD, medical oncologist, Skåne University Hospital, Lund, Sweden, agreed.

Dr. Morgan noted that healthcare professionals tend to downplay their influence over patients’ drinking habits and often don’t address these behaviors.

But that needs to change.

“We have absolutely no problem asking patients if they take supplements or vitamins or if they’re eating [healthy],” Dr. Morgan said. “So, what is the difference? Why not recommend that they cut down their alcohol intake and leave it up to everybody’s personal choice to do it or not?”

In the session, Dr. Soerjomataram highlighted the global statistics on alcohol use. IARC data show, for instance, that nearly half (46%) of the world’s population consumes alcohol, with rates higher in men (54%) than women (38%).

How much are people drinking?

Globally, on average, the amount comes to about six liters of pure ethanol per year per drinker, or about one wine bottle per week. However, consumption patterns vary widely by country. In France, people consume about 12 liters per year or about two wine bottles per week.

Dr. Soerjomataram stressed the link between alcohol consumption and cancer.

According to IARC data, heavy drinking – defined as more than 60 g/day or about six daily drinks – accounts for 47% of the alcohol-attributable cancers. Risky drinking – between 20 and 60 g/day – accounts for 29%, she explained, while moderate drinking – less than 20 g/day or about two daily drinks – accounts for roughly 14% of cases of alcohol-attributable cancers.

Globally, alcohol intake accounted for 4% of all cancers diagnosed in 2020, according to a 2021 analysis by IARC. 

In the United Kingdom alone, “alcohol drinking caused nearly 17,000 cases of cancer in 2020,” Dr. Soerjomataram said, and breast cancer made up almost one in four of those new cases.

In addition to breast cancer, six other cancer types – oral cavity, pharyngeal, laryngeal, esophageal, colorectal, and liver cancer – can be attributed to alcohol consumption, and emerging evidence suggests stomach and pancreatic cancer may be as well.

The good news, said Dr. Soerjomataram, is that long-term trends show declines in alcohol drinking in many countries, including the high wine-producing countries of France and Italy, where large reductions in consumption have been noted since the peak of intake in the 1920s.

“If it’s possible in these countries, I can imagine it’s possible elsewhere,” said Dr. Soerjomataram. 

Dr. Soerjomataram and Dr. Morgan report no relevant financial relationships.

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

There is an urgent need to raise global awareness about the direct link between alcohol consumption and cancer risk.

That message was delivered by Isabelle Soerjomataram, PhD, with the International Agency for Research on Cancer (IARC), Lyon, France, at a session devoted to alcohol and cancer at the annual meeting of the European Society for Medical Oncology.

“Global awareness about the link between alcohol and cancer continues to be very low,” Dr. Soerjomataram told the audience. “Health professionals – oncologists, nurses, medical doctors, GPs – have an important role in increasing awareness and bringing this knowledge to people, which may lead to reduced consumption.”

Session chair Gilberto Morgan, MD, medical oncologist, Skåne University Hospital, Lund, Sweden, agreed.

Dr. Morgan noted that healthcare professionals tend to downplay their influence over patients’ drinking habits and often don’t address these behaviors.

But that needs to change.

“We have absolutely no problem asking patients if they take supplements or vitamins or if they’re eating [healthy],” Dr. Morgan said. “So, what is the difference? Why not recommend that they cut down their alcohol intake and leave it up to everybody’s personal choice to do it or not?”

In the session, Dr. Soerjomataram highlighted the global statistics on alcohol use. IARC data show, for instance, that nearly half (46%) of the world’s population consumes alcohol, with rates higher in men (54%) than women (38%).

How much are people drinking?

Globally, on average, the amount comes to about six liters of pure ethanol per year per drinker, or about one wine bottle per week. However, consumption patterns vary widely by country. In France, people consume about 12 liters per year or about two wine bottles per week.

Dr. Soerjomataram stressed the link between alcohol consumption and cancer.

According to IARC data, heavy drinking – defined as more than 60 g/day or about six daily drinks – accounts for 47% of the alcohol-attributable cancers. Risky drinking – between 20 and 60 g/day – accounts for 29%, she explained, while moderate drinking – less than 20 g/day or about two daily drinks – accounts for roughly 14% of cases of alcohol-attributable cancers.

Globally, alcohol intake accounted for 4% of all cancers diagnosed in 2020, according to a 2021 analysis by IARC. 

In the United Kingdom alone, “alcohol drinking caused nearly 17,000 cases of cancer in 2020,” Dr. Soerjomataram said, and breast cancer made up almost one in four of those new cases.

In addition to breast cancer, six other cancer types – oral cavity, pharyngeal, laryngeal, esophageal, colorectal, and liver cancer – can be attributed to alcohol consumption, and emerging evidence suggests stomach and pancreatic cancer may be as well.

The good news, said Dr. Soerjomataram, is that long-term trends show declines in alcohol drinking in many countries, including the high wine-producing countries of France and Italy, where large reductions in consumption have been noted since the peak of intake in the 1920s.

“If it’s possible in these countries, I can imagine it’s possible elsewhere,” said Dr. Soerjomataram. 

Dr. Soerjomataram and Dr. Morgan report no relevant financial relationships.

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

There is an urgent need to raise global awareness about the direct link between alcohol consumption and cancer risk.

That message was delivered by Isabelle Soerjomataram, PhD, with the International Agency for Research on Cancer (IARC), Lyon, France, at a session devoted to alcohol and cancer at the annual meeting of the European Society for Medical Oncology.

“Global awareness about the link between alcohol and cancer continues to be very low,” Dr. Soerjomataram told the audience. “Health professionals – oncologists, nurses, medical doctors, GPs – have an important role in increasing awareness and bringing this knowledge to people, which may lead to reduced consumption.”

Session chair Gilberto Morgan, MD, medical oncologist, Skåne University Hospital, Lund, Sweden, agreed.

Dr. Morgan noted that healthcare professionals tend to downplay their influence over patients’ drinking habits and often don’t address these behaviors.

But that needs to change.

“We have absolutely no problem asking patients if they take supplements or vitamins or if they’re eating [healthy],” Dr. Morgan said. “So, what is the difference? Why not recommend that they cut down their alcohol intake and leave it up to everybody’s personal choice to do it or not?”

In the session, Dr. Soerjomataram highlighted the global statistics on alcohol use. IARC data show, for instance, that nearly half (46%) of the world’s population consumes alcohol, with rates higher in men (54%) than women (38%).

How much are people drinking?

Globally, on average, the amount comes to about six liters of pure ethanol per year per drinker, or about one wine bottle per week. However, consumption patterns vary widely by country. In France, people consume about 12 liters per year or about two wine bottles per week.

Dr. Soerjomataram stressed the link between alcohol consumption and cancer.

According to IARC data, heavy drinking – defined as more than 60 g/day or about six daily drinks – accounts for 47% of the alcohol-attributable cancers. Risky drinking – between 20 and 60 g/day – accounts for 29%, she explained, while moderate drinking – less than 20 g/day or about two daily drinks – accounts for roughly 14% of cases of alcohol-attributable cancers.

Globally, alcohol intake accounted for 4% of all cancers diagnosed in 2020, according to a 2021 analysis by IARC. 

In the United Kingdom alone, “alcohol drinking caused nearly 17,000 cases of cancer in 2020,” Dr. Soerjomataram said, and breast cancer made up almost one in four of those new cases.

In addition to breast cancer, six other cancer types – oral cavity, pharyngeal, laryngeal, esophageal, colorectal, and liver cancer – can be attributed to alcohol consumption, and emerging evidence suggests stomach and pancreatic cancer may be as well.

The good news, said Dr. Soerjomataram, is that long-term trends show declines in alcohol drinking in many countries, including the high wine-producing countries of France and Italy, where large reductions in consumption have been noted since the peak of intake in the 1920s.

“If it’s possible in these countries, I can imagine it’s possible elsewhere,” said Dr. Soerjomataram. 

Dr. Soerjomataram and Dr. Morgan report no relevant financial relationships.

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