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When to skip regional nodal radiation in breast cancer
SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.
Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.
Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium.
Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest.
Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.
In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone.
All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients.
Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.
Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.
The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.
The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation.
The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said.
Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.
Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.”
Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.
When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.”
“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node.
Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can.
The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
A version of this article first appeared on Medscape.com.
SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.
Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.
Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium.
Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest.
Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.
In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone.
All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients.
Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.
Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.
The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.
The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation.
The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said.
Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.
Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.”
Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.
When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.”
“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node.
Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can.
The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
A version of this article first appeared on Medscape.com.
SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.
Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.
Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium.
Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest.
Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.
In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone.
All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients.
Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.
Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.
The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.
The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation.
The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said.
Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.
Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.”
Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.
When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.”
“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node.
Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can.
The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
A version of this article first appeared on Medscape.com.
AT SABCS 2023
What will help ease the financial toll of breast cancer?
SAN ANTONIO — , new survey findings show.
Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments.
Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium.
A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.
Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.
Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.
Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).
Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).
In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.
These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups.
Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.
This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.
“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”
The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN ANTONIO — , new survey findings show.
Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments.
Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium.
A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.
Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.
Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.
Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).
Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).
In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.
These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups.
Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.
This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.
“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”
The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN ANTONIO — , new survey findings show.
Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments.
Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium.
A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.
Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.
Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.
Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).
Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).
In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.
These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups.
Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.
This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.
“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”
The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SABCS 2023
HER2+ Combo Shows Promise in Breast Cancer Brain Mets
SAN ANTONIO – (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.
Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.
“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.
Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.
The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.
To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).
The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.
There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.
“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.
Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.
“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.
She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.
The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.
SAN ANTONIO – (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.
Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.
“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.
Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.
The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.
To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).
The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.
There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.
“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.
Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.
“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.
She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.
The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.
SAN ANTONIO – (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.
Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.
“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.
Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.
The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.
To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).
The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.
There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.
“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.
Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.
“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.
She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.
The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.
AT SABCS 2023
Compelling case for skipping RT in some early breast cancers
Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy.
(1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03).
Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.
“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said.
This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.”
Results of the PROSPECT trial were published online on December 5 in The Lancet.
PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.
The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates.
Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort.
Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years.
At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%).
The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.
Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.
PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said.
The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.
Risk Tolerance and Personal Preferences
Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”
He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”
Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”
Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy.
(1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03).
Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.
“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said.
This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.”
Results of the PROSPECT trial were published online on December 5 in The Lancet.
PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.
The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates.
Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort.
Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years.
At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%).
The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.
Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.
PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said.
The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.
Risk Tolerance and Personal Preferences
Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”
He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”
Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”
Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy.
(1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03).
Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.
“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said.
This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.”
Results of the PROSPECT trial were published online on December 5 in The Lancet.
PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.
The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates.
Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort.
Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years.
At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%).
The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.
Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.
PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said.
The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.
Risk Tolerance and Personal Preferences
Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”
He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”
Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”
Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM SABCS 2023
How to address chemo-related amenorrhea in early breast cancer to help improve quality of life
in a large multicenter French cohort study.
The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.
At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.
In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).
Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).
The findings were published online November 16 in JAMA Network Open.
The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.
“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”
The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.
For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.
“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”
Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.
“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”
These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.
“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”
The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.
in a large multicenter French cohort study.
The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.
At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.
In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).
Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).
The findings were published online November 16 in JAMA Network Open.
The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.
“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”
The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.
For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.
“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”
Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.
“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”
These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.
“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”
The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.
in a large multicenter French cohort study.
The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.
At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.
In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).
Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).
The findings were published online November 16 in JAMA Network Open.
The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.
“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”
The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.
For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.
“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”
Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.
“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”
These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.
“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”
The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.
FROM JAMA NETWORK OPEN
ASTRO Updates Partial Breast Irradiation Guidance in Early Breast Cancer
The American Society for Radiation Oncology (ASTRO) has issued an updated clinical practice guideline on partial breast irradiation for women with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). The 2023 guideline, which replaces the 2017 recommendations, factors in new clinical trial data that consistently show no significant differences in overall survival, cancer-free survival, and recurrence in the same breast among patients who receive partial breast irradiation compared with whole breast irradiation. The data also indicate similar or improved side effects with partial vs whole breast irradiation.
To develop the 2023 recommendations, the Agency for Healthcare Research and Quality (AHRQ) conducted a systematic review assessing the latest clinical trial evidence, and ASTRO assembled an expert task force to determine best practices for using partial breast irradiation.
“There have been more than 10,000 women included in these randomized controlled trials, with 10 years of follow-up showing equivalency in tumor control between partial breast and whole breast radiation for appropriately selected patients,” Simona Shaitelman, MD, vice chair of the guideline task force, said in a news release.
“These data should be driving a change in practice, and partial breast radiation should be a larger part of the dialogue when we consult with patients on decisions about how best to treat their early-stage breast cancer,” added Dr. Shaitelman, professor of breast radiation oncology at the University of Texas MD Anderson Cancer Center in Houston.
What’s in the New Guidelines?
For patients with early-stage, node-negative invasive breast cancer, , including grade 1 or 2 disease, estrogen receptor (ER)-positive status, small tumor size, and age 40 or older.
In contrast, the 2017 guideline considered patients aged 50 and older suitable for partial breast irradiation and considered those in their 40s who met certain pathologic criteria “cautionary.”The updated guideline also conditionally recommends partial over whole breast irradiation if the patient has risk factors that indicate a higher likelihood of recurrence, such as grade 3 disease, ER-negative histology, or larger tumor size.
The task force does not recommend partial breast irradiation for patients with positive lymph nodes, positive surgical margins, or germline BRCA1/2 mutations or patients under 40.
Given the lack of robust data in patients with less favorable risk features, such as lymphovascular invasion or lobular histology, partial breast irradiation is conditionally not recommended for these patients.
For DCIS, the updated recommendations mirror those for early-stage breast cancer, with partial breast irradiation strongly recommended as an alternative to whole breast irradiation among patients with favorable clinical and tumor features, such as grade 1 or 2 disease and ER-positive status. Partial breast irradiation is conditionally recommended for higher grade disease or larger tumors, and not recommended for patients with positive surgical margins, BRCA mutations or those younger than 40.
In addition to relevant patient populations, the updated guidelines also address techniques and best practices for delivering partial breast irradiation.
Recommended partial breast irradiation techniques include 3-D conformal radiation therapy, intensity modulated radiation therapy, and multicatheter interstitial brachytherapy, given the evidence showing similar long-term rates of ipsilateral breast recurrence compared with whole breast irradiation.
Single-entry catheter brachytherapy is conditionally recommended, and intraoperative radiation therapy techniques are not recommended unless integrated into a prospective clinical trial or multi-institutional registry.
The guideline also outlines optimal dose, fractionation, target volume, and treatment modality with different partial breast irradiation techniques, taking toxicities and cosmesis into consideration.
“We hope that by laying out the evidence from these major trials and providing guidance on how to administer partial breast radiation, the guideline can help more oncologists feel comfortable offering this option to their patients as an alternative to whole breast radiation,” Janice Lyons, MD, of University Hospitals Seidman Cancer Center, Cleveland, Ohio, and chair of the guideline task force, said in the news release.
The guideline, developed in collaboration with the American Society of Clinical Oncology and the Society of Surgical Oncology, has been endorsed by the Canadian Association of Radiation Oncology, the European Society for Radiotherapy and Oncology, and the Royal Australian and New Zealand College of Radiologists. Guideline development was funded by ASTRO and the systematic evidence review was funded by the Patient-Centered Outcomes Research Institute. Disclosures for the task force are available with the original article.
A version of this article was first published on Medscape.com.
The American Society for Radiation Oncology (ASTRO) has issued an updated clinical practice guideline on partial breast irradiation for women with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). The 2023 guideline, which replaces the 2017 recommendations, factors in new clinical trial data that consistently show no significant differences in overall survival, cancer-free survival, and recurrence in the same breast among patients who receive partial breast irradiation compared with whole breast irradiation. The data also indicate similar or improved side effects with partial vs whole breast irradiation.
To develop the 2023 recommendations, the Agency for Healthcare Research and Quality (AHRQ) conducted a systematic review assessing the latest clinical trial evidence, and ASTRO assembled an expert task force to determine best practices for using partial breast irradiation.
“There have been more than 10,000 women included in these randomized controlled trials, with 10 years of follow-up showing equivalency in tumor control between partial breast and whole breast radiation for appropriately selected patients,” Simona Shaitelman, MD, vice chair of the guideline task force, said in a news release.
“These data should be driving a change in practice, and partial breast radiation should be a larger part of the dialogue when we consult with patients on decisions about how best to treat their early-stage breast cancer,” added Dr. Shaitelman, professor of breast radiation oncology at the University of Texas MD Anderson Cancer Center in Houston.
What’s in the New Guidelines?
For patients with early-stage, node-negative invasive breast cancer, , including grade 1 or 2 disease, estrogen receptor (ER)-positive status, small tumor size, and age 40 or older.
In contrast, the 2017 guideline considered patients aged 50 and older suitable for partial breast irradiation and considered those in their 40s who met certain pathologic criteria “cautionary.”The updated guideline also conditionally recommends partial over whole breast irradiation if the patient has risk factors that indicate a higher likelihood of recurrence, such as grade 3 disease, ER-negative histology, or larger tumor size.
The task force does not recommend partial breast irradiation for patients with positive lymph nodes, positive surgical margins, or germline BRCA1/2 mutations or patients under 40.
Given the lack of robust data in patients with less favorable risk features, such as lymphovascular invasion or lobular histology, partial breast irradiation is conditionally not recommended for these patients.
For DCIS, the updated recommendations mirror those for early-stage breast cancer, with partial breast irradiation strongly recommended as an alternative to whole breast irradiation among patients with favorable clinical and tumor features, such as grade 1 or 2 disease and ER-positive status. Partial breast irradiation is conditionally recommended for higher grade disease or larger tumors, and not recommended for patients with positive surgical margins, BRCA mutations or those younger than 40.
In addition to relevant patient populations, the updated guidelines also address techniques and best practices for delivering partial breast irradiation.
Recommended partial breast irradiation techniques include 3-D conformal radiation therapy, intensity modulated radiation therapy, and multicatheter interstitial brachytherapy, given the evidence showing similar long-term rates of ipsilateral breast recurrence compared with whole breast irradiation.
Single-entry catheter brachytherapy is conditionally recommended, and intraoperative radiation therapy techniques are not recommended unless integrated into a prospective clinical trial or multi-institutional registry.
The guideline also outlines optimal dose, fractionation, target volume, and treatment modality with different partial breast irradiation techniques, taking toxicities and cosmesis into consideration.
“We hope that by laying out the evidence from these major trials and providing guidance on how to administer partial breast radiation, the guideline can help more oncologists feel comfortable offering this option to their patients as an alternative to whole breast radiation,” Janice Lyons, MD, of University Hospitals Seidman Cancer Center, Cleveland, Ohio, and chair of the guideline task force, said in the news release.
The guideline, developed in collaboration with the American Society of Clinical Oncology and the Society of Surgical Oncology, has been endorsed by the Canadian Association of Radiation Oncology, the European Society for Radiotherapy and Oncology, and the Royal Australian and New Zealand College of Radiologists. Guideline development was funded by ASTRO and the systematic evidence review was funded by the Patient-Centered Outcomes Research Institute. Disclosures for the task force are available with the original article.
A version of this article was first published on Medscape.com.
The American Society for Radiation Oncology (ASTRO) has issued an updated clinical practice guideline on partial breast irradiation for women with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). The 2023 guideline, which replaces the 2017 recommendations, factors in new clinical trial data that consistently show no significant differences in overall survival, cancer-free survival, and recurrence in the same breast among patients who receive partial breast irradiation compared with whole breast irradiation. The data also indicate similar or improved side effects with partial vs whole breast irradiation.
To develop the 2023 recommendations, the Agency for Healthcare Research and Quality (AHRQ) conducted a systematic review assessing the latest clinical trial evidence, and ASTRO assembled an expert task force to determine best practices for using partial breast irradiation.
“There have been more than 10,000 women included in these randomized controlled trials, with 10 years of follow-up showing equivalency in tumor control between partial breast and whole breast radiation for appropriately selected patients,” Simona Shaitelman, MD, vice chair of the guideline task force, said in a news release.
“These data should be driving a change in practice, and partial breast radiation should be a larger part of the dialogue when we consult with patients on decisions about how best to treat their early-stage breast cancer,” added Dr. Shaitelman, professor of breast radiation oncology at the University of Texas MD Anderson Cancer Center in Houston.
What’s in the New Guidelines?
For patients with early-stage, node-negative invasive breast cancer, , including grade 1 or 2 disease, estrogen receptor (ER)-positive status, small tumor size, and age 40 or older.
In contrast, the 2017 guideline considered patients aged 50 and older suitable for partial breast irradiation and considered those in their 40s who met certain pathologic criteria “cautionary.”The updated guideline also conditionally recommends partial over whole breast irradiation if the patient has risk factors that indicate a higher likelihood of recurrence, such as grade 3 disease, ER-negative histology, or larger tumor size.
The task force does not recommend partial breast irradiation for patients with positive lymph nodes, positive surgical margins, or germline BRCA1/2 mutations or patients under 40.
Given the lack of robust data in patients with less favorable risk features, such as lymphovascular invasion or lobular histology, partial breast irradiation is conditionally not recommended for these patients.
For DCIS, the updated recommendations mirror those for early-stage breast cancer, with partial breast irradiation strongly recommended as an alternative to whole breast irradiation among patients with favorable clinical and tumor features, such as grade 1 or 2 disease and ER-positive status. Partial breast irradiation is conditionally recommended for higher grade disease or larger tumors, and not recommended for patients with positive surgical margins, BRCA mutations or those younger than 40.
In addition to relevant patient populations, the updated guidelines also address techniques and best practices for delivering partial breast irradiation.
Recommended partial breast irradiation techniques include 3-D conformal radiation therapy, intensity modulated radiation therapy, and multicatheter interstitial brachytherapy, given the evidence showing similar long-term rates of ipsilateral breast recurrence compared with whole breast irradiation.
Single-entry catheter brachytherapy is conditionally recommended, and intraoperative radiation therapy techniques are not recommended unless integrated into a prospective clinical trial or multi-institutional registry.
The guideline also outlines optimal dose, fractionation, target volume, and treatment modality with different partial breast irradiation techniques, taking toxicities and cosmesis into consideration.
“We hope that by laying out the evidence from these major trials and providing guidance on how to administer partial breast radiation, the guideline can help more oncologists feel comfortable offering this option to their patients as an alternative to whole breast radiation,” Janice Lyons, MD, of University Hospitals Seidman Cancer Center, Cleveland, Ohio, and chair of the guideline task force, said in the news release.
The guideline, developed in collaboration with the American Society of Clinical Oncology and the Society of Surgical Oncology, has been endorsed by the Canadian Association of Radiation Oncology, the European Society for Radiotherapy and Oncology, and the Royal Australian and New Zealand College of Radiologists. Guideline development was funded by ASTRO and the systematic evidence review was funded by the Patient-Centered Outcomes Research Institute. Disclosures for the task force are available with the original article.
A version of this article was first published on Medscape.com.
ASCO details how to manage ongoing cancer drug shortage
As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.
The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.
The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology.
In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.
And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.
The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.
The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.
More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.
In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”
Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.
In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.
“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
A version of this article appeared on Medscape.com.
As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.
The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.
The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology.
In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.
And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.
The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.
The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.
More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.
In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”
Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.
In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.
“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
A version of this article appeared on Medscape.com.
As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.
The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.
The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology.
In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.
And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.
The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.
The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.
More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.
In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”
Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.
In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.
“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
A version of this article appeared on Medscape.com.
FROM JCO ONCOLOGY PRACTICE
Avoid anti-HER2 cancer therapies during pregnancy
TOPLINE:
, according to a recent analysis.
METHODOLOGY:
- Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
- In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
- The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
- The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
- The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).
TAKEAWAY:
- Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
- Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
- The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
- Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).
IN PRACTICE:
Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.
SOURCE:
The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.
LIMITATIONS:
Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.
DISCLOSURES:
Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
A version of this article appeared on Medscape.com.
TOPLINE:
, according to a recent analysis.
METHODOLOGY:
- Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
- In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
- The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
- The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
- The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).
TAKEAWAY:
- Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
- Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
- The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
- Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).
IN PRACTICE:
Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.
SOURCE:
The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.
LIMITATIONS:
Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.
DISCLOSURES:
Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
A version of this article appeared on Medscape.com.
TOPLINE:
, according to a recent analysis.
METHODOLOGY:
- Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
- In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
- The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
- The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
- The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).
TAKEAWAY:
- Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
- Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
- The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
- Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).
IN PRACTICE:
Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.
SOURCE:
The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.
LIMITATIONS:
Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.
DISCLOSURES:
Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
A version of this article appeared on Medscape.com.
Commentary: Vaginal Estrogen Therapy, ILC, And Oral Estrogen Receptor Degraders In Breast Cancer, December 2023
Prior studies show inconsistent outcomes in patients with invasive lobular carcinoma (ILC) and data in premenopausal women is limited. The retrospective cohort study by Yoon and colleagues analyzed the data from three databases and included 225,938 premenopausal women with stage I-III ILC or invasive ductal carcinoma (IDC) in their study to evaluate survival trends in young women with ILC. In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed superior breast cancer severity score (BCSS) outcomes during the first 10 years after diagnosis (HR 0.73; P < .001); similar results were seen in the Asan Medical Center Research (AMCR) database (HR 0.50; 95% CI 0.29-0.86; P = .01). After 10 years, the trend reversed, and BCSS outcomes worsened by 80% in patients with ILC in the SEER database (HR 1.80; P < .001). This was also seen in both the Korean Breast Cancer Registry (HR 2.79; 95% CI 1.32-5.88; P = .007) and AMCR database (HR 2.23; 95% CI 1.04-4.79; P = .04). These findings remained consistent after adjusting for tumor characteristics including age, stage, tumor grade, hormone receptor status, and after controlling for treatment with chemotherapy and radiation. In addition, in the SEER database, the histologic type exerted a statistically significant time-dependent association with BCSS, with ILC showing decreasing BCSS over time (time interaction HR 1.93; 95% CI 1.78-2.10; P < .001). Furthermore, on annual hazard function analysis, the ILC annual peak event of BCSS occurred 5 years after diagnosis, whereas the IDC recurrence events peaked at 5 years before diagnosis, suggesting a higher late recurrence rate for ILC. These findings may have implications on the duration of endocrine therapy used in these patients given concern for worse long-term outcomes in premenopausal patients with ILC.
Oral selective estrogen receptor degraders (SERD) have recently emerged as a new therapeutic mechanism for patients with hormone receptor–positive breast cancer who have developed resistance to other endocrine therapies. Two of these agents, elacestrant and camizestrant, have demonstrated statistically significant progression-free survival benefit in these populations, particularly in tumors with ESR1 mutations. The efficacy of these agents in tumors with ESR1 wild-type subgroup remains uncertain. A meta-analysis by Wong and colleagues of individual patient data from four randomized clinical trials (ACELERA, AMEERA-3, EMERALD, and SERENA-2) included 1290 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer who received oral SERD or endocrine therapies (ET) of the physician's choice. In the overall cohort, oral SERD showed improved progression-free survival (PFS) outcomes compared with ET of the physician's choice (HR 0.783; 95% CI 0.681-0.900; P < .001). This was also noted in the subgroup of patients with ESR1 mutations (HR 0.557; 95% CI 0.440-0.705; P < .001); although no significant PFS benefit was observed with oral SERD in the ESR1 wild-type subgroup (HR 0.944; 95% CI 0.783-1.138; P = .543). These results suggest that the PFS benefit observed with oral SERD is mainly seen in patients with ESR1-mutated tumors, and, therefore, these drugs should be prescribed accordingly.
Additional Reference
- Cold S, Cold F, Jensen M-B, et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022;114:1347–1354. doi: 10.1093/jnci/djac112
Prior studies show inconsistent outcomes in patients with invasive lobular carcinoma (ILC) and data in premenopausal women is limited. The retrospective cohort study by Yoon and colleagues analyzed the data from three databases and included 225,938 premenopausal women with stage I-III ILC or invasive ductal carcinoma (IDC) in their study to evaluate survival trends in young women with ILC. In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed superior breast cancer severity score (BCSS) outcomes during the first 10 years after diagnosis (HR 0.73; P < .001); similar results were seen in the Asan Medical Center Research (AMCR) database (HR 0.50; 95% CI 0.29-0.86; P = .01). After 10 years, the trend reversed, and BCSS outcomes worsened by 80% in patients with ILC in the SEER database (HR 1.80; P < .001). This was also seen in both the Korean Breast Cancer Registry (HR 2.79; 95% CI 1.32-5.88; P = .007) and AMCR database (HR 2.23; 95% CI 1.04-4.79; P = .04). These findings remained consistent after adjusting for tumor characteristics including age, stage, tumor grade, hormone receptor status, and after controlling for treatment with chemotherapy and radiation. In addition, in the SEER database, the histologic type exerted a statistically significant time-dependent association with BCSS, with ILC showing decreasing BCSS over time (time interaction HR 1.93; 95% CI 1.78-2.10; P < .001). Furthermore, on annual hazard function analysis, the ILC annual peak event of BCSS occurred 5 years after diagnosis, whereas the IDC recurrence events peaked at 5 years before diagnosis, suggesting a higher late recurrence rate for ILC. These findings may have implications on the duration of endocrine therapy used in these patients given concern for worse long-term outcomes in premenopausal patients with ILC.
Oral selective estrogen receptor degraders (SERD) have recently emerged as a new therapeutic mechanism for patients with hormone receptor–positive breast cancer who have developed resistance to other endocrine therapies. Two of these agents, elacestrant and camizestrant, have demonstrated statistically significant progression-free survival benefit in these populations, particularly in tumors with ESR1 mutations. The efficacy of these agents in tumors with ESR1 wild-type subgroup remains uncertain. A meta-analysis by Wong and colleagues of individual patient data from four randomized clinical trials (ACELERA, AMEERA-3, EMERALD, and SERENA-2) included 1290 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer who received oral SERD or endocrine therapies (ET) of the physician's choice. In the overall cohort, oral SERD showed improved progression-free survival (PFS) outcomes compared with ET of the physician's choice (HR 0.783; 95% CI 0.681-0.900; P < .001). This was also noted in the subgroup of patients with ESR1 mutations (HR 0.557; 95% CI 0.440-0.705; P < .001); although no significant PFS benefit was observed with oral SERD in the ESR1 wild-type subgroup (HR 0.944; 95% CI 0.783-1.138; P = .543). These results suggest that the PFS benefit observed with oral SERD is mainly seen in patients with ESR1-mutated tumors, and, therefore, these drugs should be prescribed accordingly.
Additional Reference
- Cold S, Cold F, Jensen M-B, et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022;114:1347–1354. doi: 10.1093/jnci/djac112
Prior studies show inconsistent outcomes in patients with invasive lobular carcinoma (ILC) and data in premenopausal women is limited. The retrospective cohort study by Yoon and colleagues analyzed the data from three databases and included 225,938 premenopausal women with stage I-III ILC or invasive ductal carcinoma (IDC) in their study to evaluate survival trends in young women with ILC. In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed superior breast cancer severity score (BCSS) outcomes during the first 10 years after diagnosis (HR 0.73; P < .001); similar results were seen in the Asan Medical Center Research (AMCR) database (HR 0.50; 95% CI 0.29-0.86; P = .01). After 10 years, the trend reversed, and BCSS outcomes worsened by 80% in patients with ILC in the SEER database (HR 1.80; P < .001). This was also seen in both the Korean Breast Cancer Registry (HR 2.79; 95% CI 1.32-5.88; P = .007) and AMCR database (HR 2.23; 95% CI 1.04-4.79; P = .04). These findings remained consistent after adjusting for tumor characteristics including age, stage, tumor grade, hormone receptor status, and after controlling for treatment with chemotherapy and radiation. In addition, in the SEER database, the histologic type exerted a statistically significant time-dependent association with BCSS, with ILC showing decreasing BCSS over time (time interaction HR 1.93; 95% CI 1.78-2.10; P < .001). Furthermore, on annual hazard function analysis, the ILC annual peak event of BCSS occurred 5 years after diagnosis, whereas the IDC recurrence events peaked at 5 years before diagnosis, suggesting a higher late recurrence rate for ILC. These findings may have implications on the duration of endocrine therapy used in these patients given concern for worse long-term outcomes in premenopausal patients with ILC.
Oral selective estrogen receptor degraders (SERD) have recently emerged as a new therapeutic mechanism for patients with hormone receptor–positive breast cancer who have developed resistance to other endocrine therapies. Two of these agents, elacestrant and camizestrant, have demonstrated statistically significant progression-free survival benefit in these populations, particularly in tumors with ESR1 mutations. The efficacy of these agents in tumors with ESR1 wild-type subgroup remains uncertain. A meta-analysis by Wong and colleagues of individual patient data from four randomized clinical trials (ACELERA, AMEERA-3, EMERALD, and SERENA-2) included 1290 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer who received oral SERD or endocrine therapies (ET) of the physician's choice. In the overall cohort, oral SERD showed improved progression-free survival (PFS) outcomes compared with ET of the physician's choice (HR 0.783; 95% CI 0.681-0.900; P < .001). This was also noted in the subgroup of patients with ESR1 mutations (HR 0.557; 95% CI 0.440-0.705; P < .001); although no significant PFS benefit was observed with oral SERD in the ESR1 wild-type subgroup (HR 0.944; 95% CI 0.783-1.138; P = .543). These results suggest that the PFS benefit observed with oral SERD is mainly seen in patients with ESR1-mutated tumors, and, therefore, these drugs should be prescribed accordingly.
Additional Reference
- Cold S, Cold F, Jensen M-B, et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022;114:1347–1354. doi: 10.1093/jnci/djac112
FDA OKs new agent to block chemotherapy-induced neutropenia
Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.
The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.
The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.
The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.
During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.
The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.
The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.
A version of this article first appeared on Medscape.com.
Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.
The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.
The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.
The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.
During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.
The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.
The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.
A version of this article first appeared on Medscape.com.
Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.
The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.
The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.
The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.
During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.
The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.
The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.
A version of this article first appeared on Medscape.com.
