TBD Meeting (5163-23)

Detection of circulating tumor DNA was significantly associated with worse rates of disease-free and overall survival in patients with stage I-III breast cancer, a new meta-analysis and systematic review found.

“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.

“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Methods and results

The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.

The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.

For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.

In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
 

Results show ctDNA detection is associated with worse survival

“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.

“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”

The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
 

Detection of circulating tumor DNA was significantly associated with worse rates of disease-free and overall survival in patients with stage I-III breast cancer, a new meta-analysis and systematic review found.

“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.

“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Methods and results

The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.

The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.

For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.

In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
 

Results show ctDNA detection is associated with worse survival

“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.

“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”

The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
 

Detection of circulating tumor DNA was significantly associated with worse rates of disease-free and overall survival in patients with stage I-III breast cancer, a new meta-analysis and systematic review found.

“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.

“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Methods and results

The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.

The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.

For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.

In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
 

Results show ctDNA detection is associated with worse survival

“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.

“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”

The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
 

A new study finds that racial disparities in male breast cancer are persisting in the United States.

From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.

“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”

Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
 

Methods and results

Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).

Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).

Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
 

Findings reflect the disparities in female breast cancer

In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.

“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.

“You see similar disparities as related to mortality in Black vs. White men,” he noted.

The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.

But, he noted, the study finds that income doesn’t appear to be a factor.

In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”

No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
 

A new study finds that racial disparities in male breast cancer are persisting in the United States.

From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.

“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”

Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
 

Methods and results

Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).

Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).

Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
 

Findings reflect the disparities in female breast cancer

In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.

“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.

“You see similar disparities as related to mortality in Black vs. White men,” he noted.

The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.

But, he noted, the study finds that income doesn’t appear to be a factor.

In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”

No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
 

A new study finds that racial disparities in male breast cancer are persisting in the United States.

From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.

“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”

Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
 

Methods and results

Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).

Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).

Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
 

Findings reflect the disparities in female breast cancer

In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.

“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.

“You see similar disparities as related to mortality in Black vs. White men,” he noted.

The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.

But, he noted, the study finds that income doesn’t appear to be a factor.

In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”

No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
 

Many of the persistent problems that breast cancer survivors experience after treatment are not part of the conversation with oncologists during treatment, said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.

Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.

In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.

In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.

Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.

Shift to primary care

As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.

A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
 

Delivering the three P’s

The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .

The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.

The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.

The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.

Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.

To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.

For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.

Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.

However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.

During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
 

Engaging a patient’s partner early can be helpful

If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.

“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”

“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.

Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.

Many of the persistent problems that breast cancer survivors experience after treatment are not part of the conversation with oncologists during treatment, said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.

Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.

In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.

In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.

Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.

Shift to primary care

As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.

A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
 

Delivering the three P’s

The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .

The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.

The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.

The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.

Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.

To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.

For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.

Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.

However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.

During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
 

Engaging a patient’s partner early can be helpful

If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.

“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”

“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.

Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.

Many of the persistent problems that breast cancer survivors experience after treatment are not part of the conversation with oncologists during treatment, said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.

Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.

In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.

In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.

Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.

Shift to primary care

As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.

A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
 

Delivering the three P’s

The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .

The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.

The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.

The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.

Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.

To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.

For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.

Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.

However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.

During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
 

Engaging a patient’s partner early can be helpful

If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.

“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”

“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.

Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.

The results from a prognostic genomic assay called HER2DX convinced a group of Spanish oncologists to change treatment plans for 56% of 89 patients with HER2-positive (HER2+) early breast cancer, according to new research.

The prospective pilot study is small, and the researchers didn’t report on how the patients fared, according to a poster presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Plus, the test itself hasn’t been analyzed prospectively. But the study’s lead author, Olga Martínez-Sáez, MD, PhD, said in an interview that the 56% number is significant.

“We consider this percentage to be clinically very relevant,” said Dr. Martínez-Sáez, an oncologist at Hospital Clinic of Barcelona and the University of Barcelona. “HER2DX can change practice.”

Also in an interview, Kent Hoskins, MD, associate chief of hematology/oncology at University of Illinois at Chicago, described HER2DX as a next-generation genomic test that builds on assays developed 2 decades ago to help identify patients who would benefit – or not – from adjuvant chemotherapy.

Dr. Hoskins, who isn’t connected to the new study but has studied genomic tests for breast cancer, said the HER2DX test seeks to provide guidance to oncologists about which of several treatments are most effective in treating patients with HER2+ breast cancer.

“The overall trend in the HER2+ space is escalating therapy, and the cure rates have improved quite substantially,” he said. “But do they all need that much therapy? That’s the clinical question that this assay is addressing.”

The assay examines clinical features and the expression of 4 gene signatures, Dr. Martínez-Sáez said. It provides a risk score estimating the likelihood of recurrence plus a score that estimates the likelihood of achieving pathological complete response (pCR) with trastuzumab-based neoadjuvant therapy and an ERBB2 mRNA score.

In a retrospective 2022 study published in eBioMedicine, researchers reported that the assay “predicts response following neoadjuvant letrozole in combination with dual HER2 blockade with trastuzumab and pertuzumab in early-stage HER2-positive/hormone receptor–positive breast cancer.”

In the 2022 study, researchers wrote that assay results and other scores “might help better tailor systemic therapy in this context and identify candidates for avoiding chemotherapy, a therapy associated with short- and long-term toxicities and impact in quality of life.”

For the new study, a decision-impact analysis, researchers tracked 89 patients with HER2+ breast cancer (median age = 53 years, range 30-79, and 52% postmenopausal), the poster says. Most had T1-2 tumors (87%), negative nodes (64%), grade 2 (56%) or 3 (41%) tumors, and ductal histology (87%). And most were hormone receptor positive (65%). Seventy-eight percent of patients received neoadjuvant therapy (NAT), and 22% underwent upfront surgery.

In 56% of cases, oncologists changed their treatment decisions after getting the results of the HER2DX assays. In 59% of these cases, oncologists de-escalated therapy; in 41%, they escalated therapy, opting for more intense chemotherapy 65% of the time, according to the poster.

Clinician confidence in their decisions improved in 67% of cases, the researchers reported in their poster. Among 56 patients treated with neoadjuvant therapy who could be evaluated, “HER2DX pCR score was significantly associated with pCR (81% in pCR-medium/high and 32% in pCR-low; odds ratio=9.3, P = 0.001) independently of the rest of variables.”

Dr. Hoskins said the new report suggests that the assay can change treatment decisions, although he cautioned that “this study does not in itself establish its place in standard of care.” Large, prospective, randomized research is still needed, he said.

Dr. Martínez-Sáez said, in an interview, that the HER2DX assay should cost about as much as genomic assays for other breast cancer subtypes. These kinds of tests have cost several thousand dollars each in recent years.

What’s next? The decision impact study is ongoing. As for research into the assay itself, “prospective clinical trials are planned to demonstrate its clinical utility to de-escalate and guide therapy,” Dr. Martínez-Sáez said.

No funding is reported. Reveal Genomics is the developer of the HER2DX assay. Dr. Martinez- Saez reports financial relationships with Novartis, Eisai, Roche, and Reveal Genomics. Other study authors report multiple disclosures. Dr. Hoskins discloses non-financial research support from Agendia, which makes the MammaPrint early-breast-cancer assay.

The results from a prognostic genomic assay called HER2DX convinced a group of Spanish oncologists to change treatment plans for 56% of 89 patients with HER2-positive (HER2+) early breast cancer, according to new research.

The prospective pilot study is small, and the researchers didn’t report on how the patients fared, according to a poster presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Plus, the test itself hasn’t been analyzed prospectively. But the study’s lead author, Olga Martínez-Sáez, MD, PhD, said in an interview that the 56% number is significant.

“We consider this percentage to be clinically very relevant,” said Dr. Martínez-Sáez, an oncologist at Hospital Clinic of Barcelona and the University of Barcelona. “HER2DX can change practice.”

Also in an interview, Kent Hoskins, MD, associate chief of hematology/oncology at University of Illinois at Chicago, described HER2DX as a next-generation genomic test that builds on assays developed 2 decades ago to help identify patients who would benefit – or not – from adjuvant chemotherapy.

Dr. Hoskins, who isn’t connected to the new study but has studied genomic tests for breast cancer, said the HER2DX test seeks to provide guidance to oncologists about which of several treatments are most effective in treating patients with HER2+ breast cancer.

“The overall trend in the HER2+ space is escalating therapy, and the cure rates have improved quite substantially,” he said. “But do they all need that much therapy? That’s the clinical question that this assay is addressing.”

The assay examines clinical features and the expression of 4 gene signatures, Dr. Martínez-Sáez said. It provides a risk score estimating the likelihood of recurrence plus a score that estimates the likelihood of achieving pathological complete response (pCR) with trastuzumab-based neoadjuvant therapy and an ERBB2 mRNA score.

In a retrospective 2022 study published in eBioMedicine, researchers reported that the assay “predicts response following neoadjuvant letrozole in combination with dual HER2 blockade with trastuzumab and pertuzumab in early-stage HER2-positive/hormone receptor–positive breast cancer.”

In the 2022 study, researchers wrote that assay results and other scores “might help better tailor systemic therapy in this context and identify candidates for avoiding chemotherapy, a therapy associated with short- and long-term toxicities and impact in quality of life.”

For the new study, a decision-impact analysis, researchers tracked 89 patients with HER2+ breast cancer (median age = 53 years, range 30-79, and 52% postmenopausal), the poster says. Most had T1-2 tumors (87%), negative nodes (64%), grade 2 (56%) or 3 (41%) tumors, and ductal histology (87%). And most were hormone receptor positive (65%). Seventy-eight percent of patients received neoadjuvant therapy (NAT), and 22% underwent upfront surgery.

In 56% of cases, oncologists changed their treatment decisions after getting the results of the HER2DX assays. In 59% of these cases, oncologists de-escalated therapy; in 41%, they escalated therapy, opting for more intense chemotherapy 65% of the time, according to the poster.

Clinician confidence in their decisions improved in 67% of cases, the researchers reported in their poster. Among 56 patients treated with neoadjuvant therapy who could be evaluated, “HER2DX pCR score was significantly associated with pCR (81% in pCR-medium/high and 32% in pCR-low; odds ratio=9.3, P = 0.001) independently of the rest of variables.”

Dr. Hoskins said the new report suggests that the assay can change treatment decisions, although he cautioned that “this study does not in itself establish its place in standard of care.” Large, prospective, randomized research is still needed, he said.

Dr. Martínez-Sáez said, in an interview, that the HER2DX assay should cost about as much as genomic assays for other breast cancer subtypes. These kinds of tests have cost several thousand dollars each in recent years.

What’s next? The decision impact study is ongoing. As for research into the assay itself, “prospective clinical trials are planned to demonstrate its clinical utility to de-escalate and guide therapy,” Dr. Martínez-Sáez said.

No funding is reported. Reveal Genomics is the developer of the HER2DX assay. Dr. Martinez- Saez reports financial relationships with Novartis, Eisai, Roche, and Reveal Genomics. Other study authors report multiple disclosures. Dr. Hoskins discloses non-financial research support from Agendia, which makes the MammaPrint early-breast-cancer assay.

The results from a prognostic genomic assay called HER2DX convinced a group of Spanish oncologists to change treatment plans for 56% of 89 patients with HER2-positive (HER2+) early breast cancer, according to new research.

The prospective pilot study is small, and the researchers didn’t report on how the patients fared, according to a poster presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Plus, the test itself hasn’t been analyzed prospectively. But the study’s lead author, Olga Martínez-Sáez, MD, PhD, said in an interview that the 56% number is significant.

“We consider this percentage to be clinically very relevant,” said Dr. Martínez-Sáez, an oncologist at Hospital Clinic of Barcelona and the University of Barcelona. “HER2DX can change practice.”

Also in an interview, Kent Hoskins, MD, associate chief of hematology/oncology at University of Illinois at Chicago, described HER2DX as a next-generation genomic test that builds on assays developed 2 decades ago to help identify patients who would benefit – or not – from adjuvant chemotherapy.

Dr. Hoskins, who isn’t connected to the new study but has studied genomic tests for breast cancer, said the HER2DX test seeks to provide guidance to oncologists about which of several treatments are most effective in treating patients with HER2+ breast cancer.

“The overall trend in the HER2+ space is escalating therapy, and the cure rates have improved quite substantially,” he said. “But do they all need that much therapy? That’s the clinical question that this assay is addressing.”

The assay examines clinical features and the expression of 4 gene signatures, Dr. Martínez-Sáez said. It provides a risk score estimating the likelihood of recurrence plus a score that estimates the likelihood of achieving pathological complete response (pCR) with trastuzumab-based neoadjuvant therapy and an ERBB2 mRNA score.

In a retrospective 2022 study published in eBioMedicine, researchers reported that the assay “predicts response following neoadjuvant letrozole in combination with dual HER2 blockade with trastuzumab and pertuzumab in early-stage HER2-positive/hormone receptor–positive breast cancer.”

In the 2022 study, researchers wrote that assay results and other scores “might help better tailor systemic therapy in this context and identify candidates for avoiding chemotherapy, a therapy associated with short- and long-term toxicities and impact in quality of life.”

For the new study, a decision-impact analysis, researchers tracked 89 patients with HER2+ breast cancer (median age = 53 years, range 30-79, and 52% postmenopausal), the poster says. Most had T1-2 tumors (87%), negative nodes (64%), grade 2 (56%) or 3 (41%) tumors, and ductal histology (87%). And most were hormone receptor positive (65%). Seventy-eight percent of patients received neoadjuvant therapy (NAT), and 22% underwent upfront surgery.

In 56% of cases, oncologists changed their treatment decisions after getting the results of the HER2DX assays. In 59% of these cases, oncologists de-escalated therapy; in 41%, they escalated therapy, opting for more intense chemotherapy 65% of the time, according to the poster.

Clinician confidence in their decisions improved in 67% of cases, the researchers reported in their poster. Among 56 patients treated with neoadjuvant therapy who could be evaluated, “HER2DX pCR score was significantly associated with pCR (81% in pCR-medium/high and 32% in pCR-low; odds ratio=9.3, P = 0.001) independently of the rest of variables.”

Dr. Hoskins said the new report suggests that the assay can change treatment decisions, although he cautioned that “this study does not in itself establish its place in standard of care.” Large, prospective, randomized research is still needed, he said.

Dr. Martínez-Sáez said, in an interview, that the HER2DX assay should cost about as much as genomic assays for other breast cancer subtypes. These kinds of tests have cost several thousand dollars each in recent years.

What’s next? The decision impact study is ongoing. As for research into the assay itself, “prospective clinical trials are planned to demonstrate its clinical utility to de-escalate and guide therapy,” Dr. Martínez-Sáez said.

No funding is reported. Reveal Genomics is the developer of the HER2DX assay. Dr. Martinez- Saez reports financial relationships with Novartis, Eisai, Roche, and Reveal Genomics. Other study authors report multiple disclosures. Dr. Hoskins discloses non-financial research support from Agendia, which makes the MammaPrint early-breast-cancer assay.

Adding neoadjuvant atezolizumab to chemotherapy was associated with a significantly improved response in patients with early-stage triple-negative breast cancer, based on final data from a randomized trial.

The IMpassion031 trial showed significant improvement in pathological complete response (pCR) with the addition of atezolizumab to chemotherapy, as well as an acceptable safety profile, said Carlos H. Barrios, MD, of the Latin American Cooperative Oncology Group, Oncoclinicas, in Porto Allegre, Brazil, at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Those findings were published in the Lancet in 2020.

Heidi Splete/MDedge News

Dr. Barrios reported data from a final analysis of the IMpassion031 trial, with data on event-free survival (EFS), disease-free survival (DFS) and overall survival (OS) in the intent-to-treat (ITT) and PD-L1–positive populations.

In the study, patients with early triple-negative breast cancer (eTNBC) and a primary tumor greater than 2 cm were randomized to 840 mg of atezolizumab once every 2 weeks plus a neoadjuvant chemotherapy regimen of nab-paclitaxel 125 mg/m² once weekly for 12 weeks, followed by doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m² once every 2 weeks for 8 weeks. A total of 333 patients were randomized (165 atezolizumab and 168 placebo). Patients were stratified by stage II versus stage III, and by status of PD-L1, a protein that can predict treatment response (PD-L1 less than 1% vs. 1% or higher).

The primary endpoints (previously reported) were pathological complete response (pCR) in the ITT and PD-L1 populations. After a median follow-up of 39 months, the pCR was 58% in patients treated with atezolizumab versus 41% in those treated with neoadjuvant chemotherapy alone (P = .0044) in the ITT population, Dr. Barrios said. The added benefit from atezolizumab occurred regardless of the status of PD-L1.

Dr. Barrios reported the secondary outcomes of EFS, DFS, and OS in the intent-to-treat and PD-L1–positive populations. “This is a descriptive analysis, with no statistical comparison,” he emphasized.

The 2-year data on EFS, DFS, and OS consistently favored atezolizumab across key clinical subgroups, Dr. Barrios said. In the ITT population, 2-year EFS, DFS, and OS was 85%, 87%, and 95%, respectively, in the atezolizumab group and 80%, 83%, and 90%, respectively, in the placebo group. The results were similar, irrespective of PD-L1 status.

In the PD-L1–positive population, 2-year EFS, DFS, and OS was 89%, 91%, and 95%, respectively, in atezolizumab patients and 80%, 87%, and 91% in placebo patients.

Among patients without pCR at the time of surgery, 14 of 70 patients (20%) in the atezolizumab group and 33 of 99 patients (33%) in the placebo group received additional adjuvant systemic therapy. The most common adjunctive therapy was capecitabine.

As for safety, no new safety signals or treatment-related deaths were observed in the study. Overall, 70% of atezolizumab patients and 62% of placebo patients experienced grade 3 or 4 adverse events (AEs); 59% and 54% of which were treatment related. A total of 1% of patients in each group experienced grade 5 AEs. A total of 25% of atezolizumab patients and 20% of placebo patients experienced AEs leading to treatment discontinuation.

In a further exploratory analysis, pCR was highly predictive of long-term outcomes. Exploratory analysis of circulating tumor DNA (ctDNA) showed clearance in 89% of atezolizumab patients and 86% of placebo patients by the time of surgery.

Looking at the relationship between ctDNA, DFS, and OS, positive ctDNA was associated with a worse prognosis following surgery. As demonstrated in previous studies, pCR patients with negative ctDNA had the best DFS and OS. “In non-pCR patients with positive ctDNA, a numerical trend suggests improved overall survival with atezolizumab,” although the caveat is the very small numbers, Dr. Barrios said.

More research is needed, but in the final analysis, the significant pCR benefit seen with the addition of atezolizumab to chemotherapy for eTNBC translated into numerically improved EFS, DFS and OS, said Dr. Barrios. Additionally, “we should further analyze ctDNA to help select patients for further therapy.”

In a question-and-answer session, Dr. Barrios was asked how the results compared with other studies.

“We should not overinterpret the results,” he said. However, “what the IMpassion031 study shows is consistency; the results are aligned with previous studies addressing the same question of introducing immunotherapy,” in the patient population. Although the numbers in the IMpassion031 study did not reach statistical significance, it is important to recognize that they reflect previous research.

“In my opinion, looking at the whole field, immunotherapy is something we need to consider as part of the treatment of these patients,” said Dr. Barrios. However, more research is needed to better identify which patients do and do not need chemotherapy.
 

Phase 2 data show increased response with added atezolizumab for PD-L1–negative patients

In a second study known as ABSCG-52/ATHENE, researchers evaluated neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin for the treatment of patients with early HER2-positive breast cancer.

Heidi Splete/MDedge News

For most of these patients, the current standard of care is neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) plus poly-chemotherapy, said Gabriel Rinnerthaler, MD, of the Salzburg (Austria) Cancer Research Institute, said in his presentation at the meeting. However, de-escalation of chemotherapy has been a major focus of research in recent years, and more research is needed on a combination of anthracyclines, such as epirubicin and idarubicin, and immune-checkpoint modulators.

In the phase 2 study, the researchers randomized patients with previously untreated, histologically confirmed HER2-positive early breast cancer (defined as a clinical prognostic stage cT1c–4a-d, N0-3, M0) in a 1:1 ratio to two 3-weekly cycles of a chemotherapy-free induction phase (part 1) with TP plus 1,200 mg atezolizumab (TP-A) or TP alone.

“We hypothesized that the additive effect of immune checkpoint inhibitors plus anti-HER2 therapy and chemotherapy would not be linear,” he said.

At the end of this period, all patients underwent four cycles of TP-A in combination with epirubicin (part 2). The primary endpoint was pCR (defined as absence of invasive cancer in the breast and axillary nodes, or ypT0/Tis ypN0) in the overall study population, and a pCR of 40% was considered a positive result.

A total of 29 patients were randomized to TP-A and 29 to TP alone in nine treatment centers in Austria. The study population ranged from 33 to 82 years, with a median age of 57 years. Most patients (72.4%) had hormone receptor (HR)–positive tumors; a total of 45 patients had stage IIA cancer, and 13 had stage IIB.

The primary endpoint of pCR occurred in 35 patients overall (60.3%). In a univariate analysis, the response rates were lower in HR-positive patients, in premenopausal patients, and in histologies other than NST (invasive carcinoma of no special type), Dr. Rinnerthaler said, but none of the differences were statistically significant, likely because of the small numbers in each group.

In an exploratory analysis of the ITT population with available PD-L1 data, the pCR was 69.2% for PD-L1–negative patients and 55.2% for PD-L1–positive patients.

“We observed the highest pCR rates in PD-L1–negative patients treated in the TP-A group and the lowest in PD-L1–positive patients treated with TP alone,” Dr. Rinnerthaler said.

No new safety concerns were observed during the study, Dr. Rinnerthaler noted. AEs of grade 3 or higher occurred in 17 patients (29.3%), including 9 in the TP-A group and 8 in the TP group. The most common AEs in both groups were nausea, diarrhea, and fatigue. No AEs of special interest of grade 3 or higher (defined as immune-related AEs, cardiac disorders, or infusion-related reactions) were observed.

The study findings were limited by the small sample size, but the resulting pCR rate of 60.3% was higher than the predefined threshold of 40% and supports additional research, said Dr. Rinnerthaler.

“For HER2-positive early breast cancer, a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab, and epirubicin is highly effective and safe and merits further investigation,” he concluded.

During a question-and-answer session, Dr. Rinnerthaler was asked why pCR increased in PD-L1 negative patients.

Previous data have shown that PD-L1 is up-regulated in certain tumors, and may serve as a surrogate for sensitivity, he said. In previous studies the additional effect of atezolizumab was seen in a PD-L1–negative group.

Dr. Rinnerthaler said he hopes to clarify this question when his research team reviews biopsy data from baseline and after the induction phase.
 

Defining response is key to de-escalation

In the IMpassion031 trial, “what we saw is a tendency to better outcomes for those patients who received atezolizumab,” said Matteo Lambertini, MD, of the University of Genova (Italy), who served as discussant for the two studies. The IMpassion031 study raises the question of where we are in the use of immuno-oncology for eTNBC. The study is now one of five neoadjuvant trials in this population.

Heidi Splete/MDedge News

Dr. Lambertini cited the KEYNOTE-522 study, which showed significant results in EFS. However, sample sizes and statistical design were different between these studies. “I think we need large studies of data in the adjuvant and postneoadjuvant setting for patients with triple-negative breast cancer.”

Postneoadjuvant considerations from the IMpassion031 trial showed good outcomes with no additional benefit of an immune checkpoint inhibitors.

For those patients with a pCR, it is definitely time to de-escalate treatment,” he said. In patients without pCR, escalation is needed, but an improved definition of pCR is also needed.

With regard to the ATHENE study, “it may be considered a positive study because the threshold of 40% was reached,” he said. The question is what is the optimum chemotherapy backbone. There appears to be no added benefit to adding an immune checkpoint inhibitor.

There are needs for defining the role of immunotherapy in HER2-positive breast cancer and more biomarker research to inform patient selection and study design, he said.

Finally, “I am not sure that the addition of an immune checkpoint inhibitor can be considered a de-escalation,” he noted.

IMpassion031 was supported by F. Hoffmann–La Roche. Dr. Barrio disclosed financial relationships with numerous companies. ABSCG-52/ATHENE was supported by the Austrian Breast and Colorectal Cancer Study Group and Roche Austria. Dr. Rinnerthaler disclosed relationships with multiple companies including Amgen, Daiichi Sankyo, Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Seagen, and Pierre Fabre. Dr. Lambertini disclosed relationships with multiple companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, MSD, Seagen, Gilead, Takeda, Sandoz, Ipsen, Libbs, Knight, and Daiichi Sankyo.

Adding neoadjuvant atezolizumab to chemotherapy was associated with a significantly improved response in patients with early-stage triple-negative breast cancer, based on final data from a randomized trial.

The IMpassion031 trial showed significant improvement in pathological complete response (pCR) with the addition of atezolizumab to chemotherapy, as well as an acceptable safety profile, said Carlos H. Barrios, MD, of the Latin American Cooperative Oncology Group, Oncoclinicas, in Porto Allegre, Brazil, at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Those findings were published in the Lancet in 2020.

Heidi Splete/MDedge News

Dr. Barrios reported data from a final analysis of the IMpassion031 trial, with data on event-free survival (EFS), disease-free survival (DFS) and overall survival (OS) in the intent-to-treat (ITT) and PD-L1–positive populations.

In the study, patients with early triple-negative breast cancer (eTNBC) and a primary tumor greater than 2 cm were randomized to 840 mg of atezolizumab once every 2 weeks plus a neoadjuvant chemotherapy regimen of nab-paclitaxel 125 mg/m² once weekly for 12 weeks, followed by doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m² once every 2 weeks for 8 weeks. A total of 333 patients were randomized (165 atezolizumab and 168 placebo). Patients were stratified by stage II versus stage III, and by status of PD-L1, a protein that can predict treatment response (PD-L1 less than 1% vs. 1% or higher).

The primary endpoints (previously reported) were pathological complete response (pCR) in the ITT and PD-L1 populations. After a median follow-up of 39 months, the pCR was 58% in patients treated with atezolizumab versus 41% in those treated with neoadjuvant chemotherapy alone (P = .0044) in the ITT population, Dr. Barrios said. The added benefit from atezolizumab occurred regardless of the status of PD-L1.

Dr. Barrios reported the secondary outcomes of EFS, DFS, and OS in the intent-to-treat and PD-L1–positive populations. “This is a descriptive analysis, with no statistical comparison,” he emphasized.

The 2-year data on EFS, DFS, and OS consistently favored atezolizumab across key clinical subgroups, Dr. Barrios said. In the ITT population, 2-year EFS, DFS, and OS was 85%, 87%, and 95%, respectively, in the atezolizumab group and 80%, 83%, and 90%, respectively, in the placebo group. The results were similar, irrespective of PD-L1 status.

In the PD-L1–positive population, 2-year EFS, DFS, and OS was 89%, 91%, and 95%, respectively, in atezolizumab patients and 80%, 87%, and 91% in placebo patients.

Among patients without pCR at the time of surgery, 14 of 70 patients (20%) in the atezolizumab group and 33 of 99 patients (33%) in the placebo group received additional adjuvant systemic therapy. The most common adjunctive therapy was capecitabine.

As for safety, no new safety signals or treatment-related deaths were observed in the study. Overall, 70% of atezolizumab patients and 62% of placebo patients experienced grade 3 or 4 adverse events (AEs); 59% and 54% of which were treatment related. A total of 1% of patients in each group experienced grade 5 AEs. A total of 25% of atezolizumab patients and 20% of placebo patients experienced AEs leading to treatment discontinuation.

In a further exploratory analysis, pCR was highly predictive of long-term outcomes. Exploratory analysis of circulating tumor DNA (ctDNA) showed clearance in 89% of atezolizumab patients and 86% of placebo patients by the time of surgery.

Looking at the relationship between ctDNA, DFS, and OS, positive ctDNA was associated with a worse prognosis following surgery. As demonstrated in previous studies, pCR patients with negative ctDNA had the best DFS and OS. “In non-pCR patients with positive ctDNA, a numerical trend suggests improved overall survival with atezolizumab,” although the caveat is the very small numbers, Dr. Barrios said.

More research is needed, but in the final analysis, the significant pCR benefit seen with the addition of atezolizumab to chemotherapy for eTNBC translated into numerically improved EFS, DFS and OS, said Dr. Barrios. Additionally, “we should further analyze ctDNA to help select patients for further therapy.”

In a question-and-answer session, Dr. Barrios was asked how the results compared with other studies.

“We should not overinterpret the results,” he said. However, “what the IMpassion031 study shows is consistency; the results are aligned with previous studies addressing the same question of introducing immunotherapy,” in the patient population. Although the numbers in the IMpassion031 study did not reach statistical significance, it is important to recognize that they reflect previous research.

“In my opinion, looking at the whole field, immunotherapy is something we need to consider as part of the treatment of these patients,” said Dr. Barrios. However, more research is needed to better identify which patients do and do not need chemotherapy.
 

Phase 2 data show increased response with added atezolizumab for PD-L1–negative patients

In a second study known as ABSCG-52/ATHENE, researchers evaluated neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin for the treatment of patients with early HER2-positive breast cancer.

Heidi Splete/MDedge News

For most of these patients, the current standard of care is neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) plus poly-chemotherapy, said Gabriel Rinnerthaler, MD, of the Salzburg (Austria) Cancer Research Institute, said in his presentation at the meeting. However, de-escalation of chemotherapy has been a major focus of research in recent years, and more research is needed on a combination of anthracyclines, such as epirubicin and idarubicin, and immune-checkpoint modulators.

In the phase 2 study, the researchers randomized patients with previously untreated, histologically confirmed HER2-positive early breast cancer (defined as a clinical prognostic stage cT1c–4a-d, N0-3, M0) in a 1:1 ratio to two 3-weekly cycles of a chemotherapy-free induction phase (part 1) with TP plus 1,200 mg atezolizumab (TP-A) or TP alone.

“We hypothesized that the additive effect of immune checkpoint inhibitors plus anti-HER2 therapy and chemotherapy would not be linear,” he said.

At the end of this period, all patients underwent four cycles of TP-A in combination with epirubicin (part 2). The primary endpoint was pCR (defined as absence of invasive cancer in the breast and axillary nodes, or ypT0/Tis ypN0) in the overall study population, and a pCR of 40% was considered a positive result.

A total of 29 patients were randomized to TP-A and 29 to TP alone in nine treatment centers in Austria. The study population ranged from 33 to 82 years, with a median age of 57 years. Most patients (72.4%) had hormone receptor (HR)–positive tumors; a total of 45 patients had stage IIA cancer, and 13 had stage IIB.

The primary endpoint of pCR occurred in 35 patients overall (60.3%). In a univariate analysis, the response rates were lower in HR-positive patients, in premenopausal patients, and in histologies other than NST (invasive carcinoma of no special type), Dr. Rinnerthaler said, but none of the differences were statistically significant, likely because of the small numbers in each group.

In an exploratory analysis of the ITT population with available PD-L1 data, the pCR was 69.2% for PD-L1–negative patients and 55.2% for PD-L1–positive patients.

“We observed the highest pCR rates in PD-L1–negative patients treated in the TP-A group and the lowest in PD-L1–positive patients treated with TP alone,” Dr. Rinnerthaler said.

No new safety concerns were observed during the study, Dr. Rinnerthaler noted. AEs of grade 3 or higher occurred in 17 patients (29.3%), including 9 in the TP-A group and 8 in the TP group. The most common AEs in both groups were nausea, diarrhea, and fatigue. No AEs of special interest of grade 3 or higher (defined as immune-related AEs, cardiac disorders, or infusion-related reactions) were observed.

The study findings were limited by the small sample size, but the resulting pCR rate of 60.3% was higher than the predefined threshold of 40% and supports additional research, said Dr. Rinnerthaler.

“For HER2-positive early breast cancer, a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab, and epirubicin is highly effective and safe and merits further investigation,” he concluded.

During a question-and-answer session, Dr. Rinnerthaler was asked why pCR increased in PD-L1 negative patients.

Previous data have shown that PD-L1 is up-regulated in certain tumors, and may serve as a surrogate for sensitivity, he said. In previous studies the additional effect of atezolizumab was seen in a PD-L1–negative group.

Dr. Rinnerthaler said he hopes to clarify this question when his research team reviews biopsy data from baseline and after the induction phase.
 

Defining response is key to de-escalation

In the IMpassion031 trial, “what we saw is a tendency to better outcomes for those patients who received atezolizumab,” said Matteo Lambertini, MD, of the University of Genova (Italy), who served as discussant for the two studies. The IMpassion031 study raises the question of where we are in the use of immuno-oncology for eTNBC. The study is now one of five neoadjuvant trials in this population.

Heidi Splete/MDedge News

Dr. Lambertini cited the KEYNOTE-522 study, which showed significant results in EFS. However, sample sizes and statistical design were different between these studies. “I think we need large studies of data in the adjuvant and postneoadjuvant setting for patients with triple-negative breast cancer.”

Postneoadjuvant considerations from the IMpassion031 trial showed good outcomes with no additional benefit of an immune checkpoint inhibitors.

For those patients with a pCR, it is definitely time to de-escalate treatment,” he said. In patients without pCR, escalation is needed, but an improved definition of pCR is also needed.

With regard to the ATHENE study, “it may be considered a positive study because the threshold of 40% was reached,” he said. The question is what is the optimum chemotherapy backbone. There appears to be no added benefit to adding an immune checkpoint inhibitor.

There are needs for defining the role of immunotherapy in HER2-positive breast cancer and more biomarker research to inform patient selection and study design, he said.

Finally, “I am not sure that the addition of an immune checkpoint inhibitor can be considered a de-escalation,” he noted.

IMpassion031 was supported by F. Hoffmann–La Roche. Dr. Barrio disclosed financial relationships with numerous companies. ABSCG-52/ATHENE was supported by the Austrian Breast and Colorectal Cancer Study Group and Roche Austria. Dr. Rinnerthaler disclosed relationships with multiple companies including Amgen, Daiichi Sankyo, Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Seagen, and Pierre Fabre. Dr. Lambertini disclosed relationships with multiple companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, MSD, Seagen, Gilead, Takeda, Sandoz, Ipsen, Libbs, Knight, and Daiichi Sankyo.

Adding neoadjuvant atezolizumab to chemotherapy was associated with a significantly improved response in patients with early-stage triple-negative breast cancer, based on final data from a randomized trial.

The IMpassion031 trial showed significant improvement in pathological complete response (pCR) with the addition of atezolizumab to chemotherapy, as well as an acceptable safety profile, said Carlos H. Barrios, MD, of the Latin American Cooperative Oncology Group, Oncoclinicas, in Porto Allegre, Brazil, at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Those findings were published in the Lancet in 2020.

Heidi Splete/MDedge News

Dr. Barrios reported data from a final analysis of the IMpassion031 trial, with data on event-free survival (EFS), disease-free survival (DFS) and overall survival (OS) in the intent-to-treat (ITT) and PD-L1–positive populations.

In the study, patients with early triple-negative breast cancer (eTNBC) and a primary tumor greater than 2 cm were randomized to 840 mg of atezolizumab once every 2 weeks plus a neoadjuvant chemotherapy regimen of nab-paclitaxel 125 mg/m² once weekly for 12 weeks, followed by doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m² once every 2 weeks for 8 weeks. A total of 333 patients were randomized (165 atezolizumab and 168 placebo). Patients were stratified by stage II versus stage III, and by status of PD-L1, a protein that can predict treatment response (PD-L1 less than 1% vs. 1% or higher).

The primary endpoints (previously reported) were pathological complete response (pCR) in the ITT and PD-L1 populations. After a median follow-up of 39 months, the pCR was 58% in patients treated with atezolizumab versus 41% in those treated with neoadjuvant chemotherapy alone (P = .0044) in the ITT population, Dr. Barrios said. The added benefit from atezolizumab occurred regardless of the status of PD-L1.

Dr. Barrios reported the secondary outcomes of EFS, DFS, and OS in the intent-to-treat and PD-L1–positive populations. “This is a descriptive analysis, with no statistical comparison,” he emphasized.

The 2-year data on EFS, DFS, and OS consistently favored atezolizumab across key clinical subgroups, Dr. Barrios said. In the ITT population, 2-year EFS, DFS, and OS was 85%, 87%, and 95%, respectively, in the atezolizumab group and 80%, 83%, and 90%, respectively, in the placebo group. The results were similar, irrespective of PD-L1 status.

In the PD-L1–positive population, 2-year EFS, DFS, and OS was 89%, 91%, and 95%, respectively, in atezolizumab patients and 80%, 87%, and 91% in placebo patients.

Among patients without pCR at the time of surgery, 14 of 70 patients (20%) in the atezolizumab group and 33 of 99 patients (33%) in the placebo group received additional adjuvant systemic therapy. The most common adjunctive therapy was capecitabine.

As for safety, no new safety signals or treatment-related deaths were observed in the study. Overall, 70% of atezolizumab patients and 62% of placebo patients experienced grade 3 or 4 adverse events (AEs); 59% and 54% of which were treatment related. A total of 1% of patients in each group experienced grade 5 AEs. A total of 25% of atezolizumab patients and 20% of placebo patients experienced AEs leading to treatment discontinuation.

In a further exploratory analysis, pCR was highly predictive of long-term outcomes. Exploratory analysis of circulating tumor DNA (ctDNA) showed clearance in 89% of atezolizumab patients and 86% of placebo patients by the time of surgery.

Looking at the relationship between ctDNA, DFS, and OS, positive ctDNA was associated with a worse prognosis following surgery. As demonstrated in previous studies, pCR patients with negative ctDNA had the best DFS and OS. “In non-pCR patients with positive ctDNA, a numerical trend suggests improved overall survival with atezolizumab,” although the caveat is the very small numbers, Dr. Barrios said.

More research is needed, but in the final analysis, the significant pCR benefit seen with the addition of atezolizumab to chemotherapy for eTNBC translated into numerically improved EFS, DFS and OS, said Dr. Barrios. Additionally, “we should further analyze ctDNA to help select patients for further therapy.”

In a question-and-answer session, Dr. Barrios was asked how the results compared with other studies.

“We should not overinterpret the results,” he said. However, “what the IMpassion031 study shows is consistency; the results are aligned with previous studies addressing the same question of introducing immunotherapy,” in the patient population. Although the numbers in the IMpassion031 study did not reach statistical significance, it is important to recognize that they reflect previous research.

“In my opinion, looking at the whole field, immunotherapy is something we need to consider as part of the treatment of these patients,” said Dr. Barrios. However, more research is needed to better identify which patients do and do not need chemotherapy.
 

Phase 2 data show increased response with added atezolizumab for PD-L1–negative patients

In a second study known as ABSCG-52/ATHENE, researchers evaluated neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin for the treatment of patients with early HER2-positive breast cancer.

Heidi Splete/MDedge News

For most of these patients, the current standard of care is neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) plus poly-chemotherapy, said Gabriel Rinnerthaler, MD, of the Salzburg (Austria) Cancer Research Institute, said in his presentation at the meeting. However, de-escalation of chemotherapy has been a major focus of research in recent years, and more research is needed on a combination of anthracyclines, such as epirubicin and idarubicin, and immune-checkpoint modulators.

In the phase 2 study, the researchers randomized patients with previously untreated, histologically confirmed HER2-positive early breast cancer (defined as a clinical prognostic stage cT1c–4a-d, N0-3, M0) in a 1:1 ratio to two 3-weekly cycles of a chemotherapy-free induction phase (part 1) with TP plus 1,200 mg atezolizumab (TP-A) or TP alone.

“We hypothesized that the additive effect of immune checkpoint inhibitors plus anti-HER2 therapy and chemotherapy would not be linear,” he said.

At the end of this period, all patients underwent four cycles of TP-A in combination with epirubicin (part 2). The primary endpoint was pCR (defined as absence of invasive cancer in the breast and axillary nodes, or ypT0/Tis ypN0) in the overall study population, and a pCR of 40% was considered a positive result.

A total of 29 patients were randomized to TP-A and 29 to TP alone in nine treatment centers in Austria. The study population ranged from 33 to 82 years, with a median age of 57 years. Most patients (72.4%) had hormone receptor (HR)–positive tumors; a total of 45 patients had stage IIA cancer, and 13 had stage IIB.

The primary endpoint of pCR occurred in 35 patients overall (60.3%). In a univariate analysis, the response rates were lower in HR-positive patients, in premenopausal patients, and in histologies other than NST (invasive carcinoma of no special type), Dr. Rinnerthaler said, but none of the differences were statistically significant, likely because of the small numbers in each group.

In an exploratory analysis of the ITT population with available PD-L1 data, the pCR was 69.2% for PD-L1–negative patients and 55.2% for PD-L1–positive patients.

“We observed the highest pCR rates in PD-L1–negative patients treated in the TP-A group and the lowest in PD-L1–positive patients treated with TP alone,” Dr. Rinnerthaler said.

No new safety concerns were observed during the study, Dr. Rinnerthaler noted. AEs of grade 3 or higher occurred in 17 patients (29.3%), including 9 in the TP-A group and 8 in the TP group. The most common AEs in both groups were nausea, diarrhea, and fatigue. No AEs of special interest of grade 3 or higher (defined as immune-related AEs, cardiac disorders, or infusion-related reactions) were observed.

The study findings were limited by the small sample size, but the resulting pCR rate of 60.3% was higher than the predefined threshold of 40% and supports additional research, said Dr. Rinnerthaler.

“For HER2-positive early breast cancer, a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab, and epirubicin is highly effective and safe and merits further investigation,” he concluded.

During a question-and-answer session, Dr. Rinnerthaler was asked why pCR increased in PD-L1 negative patients.

Previous data have shown that PD-L1 is up-regulated in certain tumors, and may serve as a surrogate for sensitivity, he said. In previous studies the additional effect of atezolizumab was seen in a PD-L1–negative group.

Dr. Rinnerthaler said he hopes to clarify this question when his research team reviews biopsy data from baseline and after the induction phase.
 

Defining response is key to de-escalation

In the IMpassion031 trial, “what we saw is a tendency to better outcomes for those patients who received atezolizumab,” said Matteo Lambertini, MD, of the University of Genova (Italy), who served as discussant for the two studies. The IMpassion031 study raises the question of where we are in the use of immuno-oncology for eTNBC. The study is now one of five neoadjuvant trials in this population.

Heidi Splete/MDedge News

Dr. Lambertini cited the KEYNOTE-522 study, which showed significant results in EFS. However, sample sizes and statistical design were different between these studies. “I think we need large studies of data in the adjuvant and postneoadjuvant setting for patients with triple-negative breast cancer.”

Postneoadjuvant considerations from the IMpassion031 trial showed good outcomes with no additional benefit of an immune checkpoint inhibitors.

For those patients with a pCR, it is definitely time to de-escalate treatment,” he said. In patients without pCR, escalation is needed, but an improved definition of pCR is also needed.

With regard to the ATHENE study, “it may be considered a positive study because the threshold of 40% was reached,” he said. The question is what is the optimum chemotherapy backbone. There appears to be no added benefit to adding an immune checkpoint inhibitor.

There are needs for defining the role of immunotherapy in HER2-positive breast cancer and more biomarker research to inform patient selection and study design, he said.

Finally, “I am not sure that the addition of an immune checkpoint inhibitor can be considered a de-escalation,” he noted.

IMpassion031 was supported by F. Hoffmann–La Roche. Dr. Barrio disclosed financial relationships with numerous companies. ABSCG-52/ATHENE was supported by the Austrian Breast and Colorectal Cancer Study Group and Roche Austria. Dr. Rinnerthaler disclosed relationships with multiple companies including Amgen, Daiichi Sankyo, Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Seagen, and Pierre Fabre. Dr. Lambertini disclosed relationships with multiple companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, MSD, Seagen, Gilead, Takeda, Sandoz, Ipsen, Libbs, Knight, and Daiichi Sankyo.

A single dose of a new antibody-drug conjugate known as patritumab deruxtecan provoked a response in nearly one-third of patients with HR-positive/HER2-negative or triple-negative breast cancer, according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

Heidi Splete/MDedge News

Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.

Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.

Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.

In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.

In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.

Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.

All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.

At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049). 

In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).

Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.

HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.

A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.

To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.

During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
 

ICARUS-BREAST01

In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.

Heidi Splete/MDedge News

The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.

After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.

As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.

Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.

“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.

In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.

Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.

In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.

Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.

Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
 

Early results merit further exploration

Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.

Heidi Splete/MDedge News

“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.

In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.

“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.

The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.

“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”

In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.

The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.

A single dose of a new antibody-drug conjugate known as patritumab deruxtecan provoked a response in nearly one-third of patients with HR-positive/HER2-negative or triple-negative breast cancer, according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

Heidi Splete/MDedge News

Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.

Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.

Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.

In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.

In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.

Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.

All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.

At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049). 

In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).

Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.

HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.

A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.

To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.

During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
 

ICARUS-BREAST01

In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.

Heidi Splete/MDedge News

The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.

After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.

As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.

Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.

“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.

In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.

Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.

In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.

Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.

Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
 

Early results merit further exploration

Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.

Heidi Splete/MDedge News

“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.

In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.

“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.

The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.

“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”

In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.

The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.

A single dose of a new antibody-drug conjugate known as patritumab deruxtecan provoked a response in nearly one-third of patients with HR-positive/HER2-negative or triple-negative breast cancer, according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

Heidi Splete/MDedge News

Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.

Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.

Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.

In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.

In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.

Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.

All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.

At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049). 

In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).

Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.

HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.

A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.

To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.

During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
 

ICARUS-BREAST01

In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.

Heidi Splete/MDedge News

The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.

After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.

As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.

Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.

“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.

In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.

Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.

In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.

Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.

Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
 

Early results merit further exploration

Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.

Heidi Splete/MDedge News

“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.

In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.

“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.

The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.

“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”

In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.

The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.

A safety analysis following a landmark randomized phase 3 trial confirms that vomiting and nausea are quite common in patients who take the drug trastuzumab deruxtecan (T-DXd; Enhertu) to treat HER2-low metastatic breast cancer. Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.

In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”

However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.

For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”

Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).

A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.

Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)

ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.

Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.

In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”

In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”

Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”

The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.

The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).

The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.

A safety analysis following a landmark randomized phase 3 trial confirms that vomiting and nausea are quite common in patients who take the drug trastuzumab deruxtecan (T-DXd; Enhertu) to treat HER2-low metastatic breast cancer. Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.

In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”

However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.

For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”

Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).

A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.

Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)

ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.

Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.

In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”

In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”

Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”

The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.

The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).

The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.

A safety analysis following a landmark randomized phase 3 trial confirms that vomiting and nausea are quite common in patients who take the drug trastuzumab deruxtecan (T-DXd; Enhertu) to treat HER2-low metastatic breast cancer. Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.

In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”

However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.

For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”

Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).

A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.

Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)

ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.

Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.

In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”

In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”

Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”

The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.

The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).

The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.

In postmenopausal women with hormone receptor–positive breast cancer, overweight and obesity were overall predictors of lower disease-free survival, but body mass index had no apparent association with the effect of extended endocrine therapy on disease-free survival, new data suggest.

Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.

Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.

The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.

Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (30 kg/m² or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.

DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).

“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.

In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.

The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.

In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.

When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
 

Data draw attention to quality of life and lifestyle factors

The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.

Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.

Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.

“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.

The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.

In postmenopausal women with hormone receptor–positive breast cancer, overweight and obesity were overall predictors of lower disease-free survival, but body mass index had no apparent association with the effect of extended endocrine therapy on disease-free survival, new data suggest.

Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.

Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.

The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.

Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (30 kg/m² or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.

DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).

“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.

In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.

The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.

In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.

When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
 

Data draw attention to quality of life and lifestyle factors

The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.

Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.

Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.

“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.

The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.

In postmenopausal women with hormone receptor–positive breast cancer, overweight and obesity were overall predictors of lower disease-free survival, but body mass index had no apparent association with the effect of extended endocrine therapy on disease-free survival, new data suggest.

Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.

Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.

The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.

Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (30 kg/m² or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.

DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).

“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.

In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.

The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.

In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.

When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
 

Data draw attention to quality of life and lifestyle factors

The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.

Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.

Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.

“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.

The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.