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FDA Removes Harmful Chemicals From Food Packaging
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
What Happens to Surgery Candidates with BHDs and Cancer?
based on data from a new study of nearly 700,000 individuals.
The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
What is Known About BHDs and Cancer?
Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.
Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.
A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.
Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer.
Why Was It Important to Conduct This Study?
“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.
What Does the New Study Add?
In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.
Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).
Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).
Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”
Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?
The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.
“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
What Can Oncologists Do to Help?
The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.
“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.
Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
What Are the Limitations?
The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.
What Are the Next Steps for Research?
The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.
“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.
The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.
based on data from a new study of nearly 700,000 individuals.
The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
What is Known About BHDs and Cancer?
Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.
Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.
A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.
Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer.
Why Was It Important to Conduct This Study?
“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.
What Does the New Study Add?
In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.
Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).
Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).
Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”
Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?
The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.
“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
What Can Oncologists Do to Help?
The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.
“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.
Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
What Are the Limitations?
The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.
What Are the Next Steps for Research?
The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.
“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.
The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.
based on data from a new study of nearly 700,000 individuals.
The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
What is Known About BHDs and Cancer?
Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.
Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.
A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.
Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer.
Why Was It Important to Conduct This Study?
“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.
What Does the New Study Add?
In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.
Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).
Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).
Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”
Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?
The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.
“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
What Can Oncologists Do to Help?
The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.
“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.
Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
What Are the Limitations?
The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.
What Are the Next Steps for Research?
The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.
“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.
The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.
FROM JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
Are Food Emulsifiers Associated With Increased Cancer Risk?
Food emulsifiers are among the most widespread food additives.
Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.
Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.
Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.
The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.
In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).
Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.
In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.
The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.
It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Food emulsifiers are among the most widespread food additives.
Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.
Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.
Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.
The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.
In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).
Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.
In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.
The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.
It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Food emulsifiers are among the most widespread food additives.
Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.
Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.
Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.
The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.
In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).
Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.
In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.
The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.
It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Democratic Lawmakers Press Pfizer on Chemotherapy Drug Shortages
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
Unleashing Our Immune Response to Quash Cancer
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
Robotic Mastectomy Is Feasible, But Is It Safe?
a type of conservative mastectomy preserving the skin and nipple-areola complex. The new findings potentially expand the application of robotic surgery to a larger patient population but doubts about the safety of this approach linger.
Robotic Mastectomy
The first surgeries involving the Da Vinci robotic surgeon for breast removal date to 2015. Multiport robotic surgery faces significant obstacles in this field, however. Feasibility studies have primarily focused on women with small breasts, corresponding to cup size C or smaller.
In the study that was published in JAMA Surgery, surgeons used the more cost-effective single-port platform for bilateral NSM procedures. Among the 20 patients included in the analysis (age, 29-63 years), 11 underwent prophylactic mastectomy (for a high risk for cancer) and 9 had mastectomy for breast tumors. Breast sizes ranged from A cup to D cup.
The duration of the procedure, from skin incision to suture for both breasts, ranged from 205 to 351 minutes (median, 277 minutes). No immediate operative complications (eg, hematoma) occurred, and there was no need for conversion to open surgery in any case. Over the 36-month follow-up, there were no recurrences. About 95% of patients retained skin sensitivity and 55% retained nipple sensitivity.
Unanswered Questions
In an accompanying article, Monica Morrow, MD, director of surgical breast oncology at the Memorial Sloan-Kettering Cancer Center in New York, acknowledged that the new evidence confirms the surgical approach’s feasibility but deems it insufficient to adopt it lightly. “At this point, the issue is not whether robotic mastectomy can be done but whether there is sufficient information about its oncologic safety that it should be done,” she wrote.
In a 2019 statement that was updated in 2021, the US Food and Drug Administration stated, “The safety and effectiveness of using robotically assisted surgical devices in mastectomy procedures or in the prevention or treatment of breast cancer have not been established.” The significance of this caution is underscored by the experience with laparoscopic and robotic radical hysterectomies. These procedures were widely adopted until a randomized prospective study demonstrated lower disease-free and overall survival for the minimally invasive approach compared with open surgery.
The University of Texas surgeons stated that acceptable safety and oncological outcomes for robotic NSM compared with conventional NSM had been demonstrated. They cited two trials with 238 cases and a median follow-up of less than 3 years. Dr. Morrow wrote, “While these reports provide reassurance that gross residual tumor is not being left behind, they do not address the issue of failure to remove all of the breast tissue due to thick skin flaps, with the potential for development of late recurrence or new cancers.” It is worth noting that even with the traditional surgical approach, the 5-year local recurrence rate after NSM is approximately double when observed with shorter follow-ups.
According to Dr. Morrow, the high rate of sensory preservation observed with robotic surgery, a desirable outcome for patients, is also a cause for concern. “While this may be due to incision placement or minimal skin flap retraction, as suggested by the authors, it is equally plausible that this could be due to thick skin flaps with preservation of the terminal branches of the fourth intercostal nerve.”
Therefore, more information on long-term oncological outcomes in a large number of patients will be necessary to confirm the safety of the procedure. In addition, measuring patient-reported outcomes will be useful in demonstrating that the benefits of the procedure outweigh increased operating times and costs.
This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.
a type of conservative mastectomy preserving the skin and nipple-areola complex. The new findings potentially expand the application of robotic surgery to a larger patient population but doubts about the safety of this approach linger.
Robotic Mastectomy
The first surgeries involving the Da Vinci robotic surgeon for breast removal date to 2015. Multiport robotic surgery faces significant obstacles in this field, however. Feasibility studies have primarily focused on women with small breasts, corresponding to cup size C or smaller.
In the study that was published in JAMA Surgery, surgeons used the more cost-effective single-port platform for bilateral NSM procedures. Among the 20 patients included in the analysis (age, 29-63 years), 11 underwent prophylactic mastectomy (for a high risk for cancer) and 9 had mastectomy for breast tumors. Breast sizes ranged from A cup to D cup.
The duration of the procedure, from skin incision to suture for both breasts, ranged from 205 to 351 minutes (median, 277 minutes). No immediate operative complications (eg, hematoma) occurred, and there was no need for conversion to open surgery in any case. Over the 36-month follow-up, there were no recurrences. About 95% of patients retained skin sensitivity and 55% retained nipple sensitivity.
Unanswered Questions
In an accompanying article, Monica Morrow, MD, director of surgical breast oncology at the Memorial Sloan-Kettering Cancer Center in New York, acknowledged that the new evidence confirms the surgical approach’s feasibility but deems it insufficient to adopt it lightly. “At this point, the issue is not whether robotic mastectomy can be done but whether there is sufficient information about its oncologic safety that it should be done,” she wrote.
In a 2019 statement that was updated in 2021, the US Food and Drug Administration stated, “The safety and effectiveness of using robotically assisted surgical devices in mastectomy procedures or in the prevention or treatment of breast cancer have not been established.” The significance of this caution is underscored by the experience with laparoscopic and robotic radical hysterectomies. These procedures were widely adopted until a randomized prospective study demonstrated lower disease-free and overall survival for the minimally invasive approach compared with open surgery.
The University of Texas surgeons stated that acceptable safety and oncological outcomes for robotic NSM compared with conventional NSM had been demonstrated. They cited two trials with 238 cases and a median follow-up of less than 3 years. Dr. Morrow wrote, “While these reports provide reassurance that gross residual tumor is not being left behind, they do not address the issue of failure to remove all of the breast tissue due to thick skin flaps, with the potential for development of late recurrence or new cancers.” It is worth noting that even with the traditional surgical approach, the 5-year local recurrence rate after NSM is approximately double when observed with shorter follow-ups.
According to Dr. Morrow, the high rate of sensory preservation observed with robotic surgery, a desirable outcome for patients, is also a cause for concern. “While this may be due to incision placement or minimal skin flap retraction, as suggested by the authors, it is equally plausible that this could be due to thick skin flaps with preservation of the terminal branches of the fourth intercostal nerve.”
Therefore, more information on long-term oncological outcomes in a large number of patients will be necessary to confirm the safety of the procedure. In addition, measuring patient-reported outcomes will be useful in demonstrating that the benefits of the procedure outweigh increased operating times and costs.
This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.
a type of conservative mastectomy preserving the skin and nipple-areola complex. The new findings potentially expand the application of robotic surgery to a larger patient population but doubts about the safety of this approach linger.
Robotic Mastectomy
The first surgeries involving the Da Vinci robotic surgeon for breast removal date to 2015. Multiport robotic surgery faces significant obstacles in this field, however. Feasibility studies have primarily focused on women with small breasts, corresponding to cup size C or smaller.
In the study that was published in JAMA Surgery, surgeons used the more cost-effective single-port platform for bilateral NSM procedures. Among the 20 patients included in the analysis (age, 29-63 years), 11 underwent prophylactic mastectomy (for a high risk for cancer) and 9 had mastectomy for breast tumors. Breast sizes ranged from A cup to D cup.
The duration of the procedure, from skin incision to suture for both breasts, ranged from 205 to 351 minutes (median, 277 minutes). No immediate operative complications (eg, hematoma) occurred, and there was no need for conversion to open surgery in any case. Over the 36-month follow-up, there were no recurrences. About 95% of patients retained skin sensitivity and 55% retained nipple sensitivity.
Unanswered Questions
In an accompanying article, Monica Morrow, MD, director of surgical breast oncology at the Memorial Sloan-Kettering Cancer Center in New York, acknowledged that the new evidence confirms the surgical approach’s feasibility but deems it insufficient to adopt it lightly. “At this point, the issue is not whether robotic mastectomy can be done but whether there is sufficient information about its oncologic safety that it should be done,” she wrote.
In a 2019 statement that was updated in 2021, the US Food and Drug Administration stated, “The safety and effectiveness of using robotically assisted surgical devices in mastectomy procedures or in the prevention or treatment of breast cancer have not been established.” The significance of this caution is underscored by the experience with laparoscopic and robotic radical hysterectomies. These procedures were widely adopted until a randomized prospective study demonstrated lower disease-free and overall survival for the minimally invasive approach compared with open surgery.
The University of Texas surgeons stated that acceptable safety and oncological outcomes for robotic NSM compared with conventional NSM had been demonstrated. They cited two trials with 238 cases and a median follow-up of less than 3 years. Dr. Morrow wrote, “While these reports provide reassurance that gross residual tumor is not being left behind, they do not address the issue of failure to remove all of the breast tissue due to thick skin flaps, with the potential for development of late recurrence or new cancers.” It is worth noting that even with the traditional surgical approach, the 5-year local recurrence rate after NSM is approximately double when observed with shorter follow-ups.
According to Dr. Morrow, the high rate of sensory preservation observed with robotic surgery, a desirable outcome for patients, is also a cause for concern. “While this may be due to incision placement or minimal skin flap retraction, as suggested by the authors, it is equally plausible that this could be due to thick skin flaps with preservation of the terminal branches of the fourth intercostal nerve.”
Therefore, more information on long-term oncological outcomes in a large number of patients will be necessary to confirm the safety of the procedure. In addition, measuring patient-reported outcomes will be useful in demonstrating that the benefits of the procedure outweigh increased operating times and costs.
This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.
FROM JAMA SURGERY
Dana-Farber Moves to Retract, Correct Dozens of Cancer Papers Amid Allegations
News of the investigation follows a blog post by British molecular biologist Sholto David, MD, who flagged almost 60 papers published between 1997 and 2017 that contained image manipulation and other errors. Some of the papers were published by Dana-Farber’s chief executive officer, Laurie Glimcher, MD, and chief operating officer, William Hahn, MD, on topics including multiple myeloma and immune cells.
Mr. David, who blogs about research integrity, highlighted numerous errors and irregularities, including copying and pasting images across multiple experiments to represent different days within the same experiment, sometimes rotating or stretching images.
In one case, Mr. David equated the manipulation with tactics used by “hapless Chinese papermills” and concluded that “a swathe of research coming out of [Dana-Farber] authored by the most senior researchers and managers appears to be hopelessly corrupt with errors that are obvious from just a cursory reading the papers.”
“Imagine what mistakes might be found in the raw data if anyone was allowed to look!” he wrote.
Barrett Rollins, MD, PhD, Dana-Farber Cancer Institute’s research integrity officer, declined to comment on whether the errors represent scientific misconduct, according to STAT. Rollins told ScienceInsider that the “presence of image discrepancies in a paper is not evidence of an author’s intent to deceive.”
Access to new artificial intelligence tools is making it easier for data sleuths, like Mr. David, to unearth data manipulation and errors.
The current investigation closely follows two other investigations into the published work of Harvard University’s former president, Claudine Gay, and Stanford University’s former president, Marc Tessier-Lavigne, which led both to resign their posts.
A version of this article appeared on Medscape.com.
News of the investigation follows a blog post by British molecular biologist Sholto David, MD, who flagged almost 60 papers published between 1997 and 2017 that contained image manipulation and other errors. Some of the papers were published by Dana-Farber’s chief executive officer, Laurie Glimcher, MD, and chief operating officer, William Hahn, MD, on topics including multiple myeloma and immune cells.
Mr. David, who blogs about research integrity, highlighted numerous errors and irregularities, including copying and pasting images across multiple experiments to represent different days within the same experiment, sometimes rotating or stretching images.
In one case, Mr. David equated the manipulation with tactics used by “hapless Chinese papermills” and concluded that “a swathe of research coming out of [Dana-Farber] authored by the most senior researchers and managers appears to be hopelessly corrupt with errors that are obvious from just a cursory reading the papers.”
“Imagine what mistakes might be found in the raw data if anyone was allowed to look!” he wrote.
Barrett Rollins, MD, PhD, Dana-Farber Cancer Institute’s research integrity officer, declined to comment on whether the errors represent scientific misconduct, according to STAT. Rollins told ScienceInsider that the “presence of image discrepancies in a paper is not evidence of an author’s intent to deceive.”
Access to new artificial intelligence tools is making it easier for data sleuths, like Mr. David, to unearth data manipulation and errors.
The current investigation closely follows two other investigations into the published work of Harvard University’s former president, Claudine Gay, and Stanford University’s former president, Marc Tessier-Lavigne, which led both to resign their posts.
A version of this article appeared on Medscape.com.
News of the investigation follows a blog post by British molecular biologist Sholto David, MD, who flagged almost 60 papers published between 1997 and 2017 that contained image manipulation and other errors. Some of the papers were published by Dana-Farber’s chief executive officer, Laurie Glimcher, MD, and chief operating officer, William Hahn, MD, on topics including multiple myeloma and immune cells.
Mr. David, who blogs about research integrity, highlighted numerous errors and irregularities, including copying and pasting images across multiple experiments to represent different days within the same experiment, sometimes rotating or stretching images.
In one case, Mr. David equated the manipulation with tactics used by “hapless Chinese papermills” and concluded that “a swathe of research coming out of [Dana-Farber] authored by the most senior researchers and managers appears to be hopelessly corrupt with errors that are obvious from just a cursory reading the papers.”
“Imagine what mistakes might be found in the raw data if anyone was allowed to look!” he wrote.
Barrett Rollins, MD, PhD, Dana-Farber Cancer Institute’s research integrity officer, declined to comment on whether the errors represent scientific misconduct, according to STAT. Rollins told ScienceInsider that the “presence of image discrepancies in a paper is not evidence of an author’s intent to deceive.”
Access to new artificial intelligence tools is making it easier for data sleuths, like Mr. David, to unearth data manipulation and errors.
The current investigation closely follows two other investigations into the published work of Harvard University’s former president, Claudine Gay, and Stanford University’s former president, Marc Tessier-Lavigne, which led both to resign their posts.
A version of this article appeared on Medscape.com.
Radiation Oncologists Fight for Payment Reform Amid Cuts
The American Society for Radiation Oncology (ASTRO) recently announced its partnership with three other groups — the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology — to change how the specialty is paid for services.
Over the past decade, radiation oncologists have seen a 23% drop in Medicare reimbursement for radiation therapy services, with more cuts to come, according to a press release from ASTRO.
Traditionally, Medicare has reimbursed on the basis of the fraction of radiation delivered. But with moves toward hypofractionated regimens, deescalated therapy, and other changes in the field, reimbursement has continued to dwindle.
The cuts have led to practice consolidation and closures that threaten patient access especially in rural and underserved areas, a spokesperson for the group told this news organization.
To reverse this trend, ASTRO recently proposed the Radiation Oncology Case Rate program, a legislative initiative to base reimbursements on patient volumes instead of fractions delivered.
ASTRO is currently drafting a congressional bill to change the current payment structure, which “has become untenable,” the spokesperson said.
A version of this article appeared on Medscape.com.
The American Society for Radiation Oncology (ASTRO) recently announced its partnership with three other groups — the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology — to change how the specialty is paid for services.
Over the past decade, radiation oncologists have seen a 23% drop in Medicare reimbursement for radiation therapy services, with more cuts to come, according to a press release from ASTRO.
Traditionally, Medicare has reimbursed on the basis of the fraction of radiation delivered. But with moves toward hypofractionated regimens, deescalated therapy, and other changes in the field, reimbursement has continued to dwindle.
The cuts have led to practice consolidation and closures that threaten patient access especially in rural and underserved areas, a spokesperson for the group told this news organization.
To reverse this trend, ASTRO recently proposed the Radiation Oncology Case Rate program, a legislative initiative to base reimbursements on patient volumes instead of fractions delivered.
ASTRO is currently drafting a congressional bill to change the current payment structure, which “has become untenable,” the spokesperson said.
A version of this article appeared on Medscape.com.
The American Society for Radiation Oncology (ASTRO) recently announced its partnership with three other groups — the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology — to change how the specialty is paid for services.
Over the past decade, radiation oncologists have seen a 23% drop in Medicare reimbursement for radiation therapy services, with more cuts to come, according to a press release from ASTRO.
Traditionally, Medicare has reimbursed on the basis of the fraction of radiation delivered. But with moves toward hypofractionated regimens, deescalated therapy, and other changes in the field, reimbursement has continued to dwindle.
The cuts have led to practice consolidation and closures that threaten patient access especially in rural and underserved areas, a spokesperson for the group told this news organization.
To reverse this trend, ASTRO recently proposed the Radiation Oncology Case Rate program, a legislative initiative to base reimbursements on patient volumes instead of fractions delivered.
ASTRO is currently drafting a congressional bill to change the current payment structure, which “has become untenable,” the spokesperson said.
A version of this article appeared on Medscape.com.
Updates on Investigational Treatments for HR-Positive, HER2-Negative Breast Cancer
Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023.
A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD.
TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy
Study synopsis
Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial.
Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results:
In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)
At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent
In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients
In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively
At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd
The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.
EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging
Study synopsis
The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study.
Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate.
The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events:
The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)
The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)
The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).
In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment
In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus
In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib
Regarding efficacy:
The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively
The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively
Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer.
OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities
Study synopsis
OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.
Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date:
Grade 3 neutropenia occurred in 55% of participants
There were no grade 4 treatment-related adverse events and no dose-limiting toxicities
OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study
Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages
Investigators observed antitumor activity, including partial responses
Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation.
Conclusions
These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.
Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023.
A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD.
TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy
Study synopsis
Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial.
Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results:
In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)
At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent
In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients
In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively
At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd
The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.
EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging
Study synopsis
The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study.
Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate.
The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events:
The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)
The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)
The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).
In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment
In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus
In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib
Regarding efficacy:
The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively
The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively
Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer.
OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities
Study synopsis
OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.
Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date:
Grade 3 neutropenia occurred in 55% of participants
There were no grade 4 treatment-related adverse events and no dose-limiting toxicities
OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study
Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages
Investigators observed antitumor activity, including partial responses
Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation.
Conclusions
These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.
Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023.
A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD.
TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy
Study synopsis
Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial.
Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results:
In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)
At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent
In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients
In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively
At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd
The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.
EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging
Study synopsis
The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study.
Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate.
The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events:
The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)
The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)
The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).
In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment
In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus
In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib
Regarding efficacy:
The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively
The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively
Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer.
OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities
Study synopsis
OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.
Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date:
Grade 3 neutropenia occurred in 55% of participants
There were no grade 4 treatment-related adverse events and no dose-limiting toxicities
OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study
Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages
Investigators observed antitumor activity, including partial responses
Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation.
Conclusions
These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.
Dato-DXd trumps chemo in advanced HR+/HER2– breast cancer
The investigational anti-body drug conjugate (ADC) 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) 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) 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.
FROM ESMO CONGRESS 2023