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Statin Use May Extend Life for Early Breast Cancer Patients
Previous research examining the association between cholesterol and breast cancer metabolism suggests that cholesterol-lowering medications such as statins may improve outcomes in breast cancer patients, Sixten Harborg, a medical student and PhD student at Aarhus University, Denmark, said in a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
In addition, cardiovascular-related death is the second most common cause of death for breast cancer survivors, and given the survival rates in early breast cancer, there is a demand for cardioprotective initiatives and maintenance of cardioprotective drugs after diagnosis, he said in an interview.
What Is Known About Statins and Breast Cancer?
Statins are the most common drugs used to lower cholesterol and may deprive tumor cells of the cholesterol needed for cell membrane synthesis, Mr. Harborg said in his presentation.
Data from a randomized trial published in the Journal of Clinical Oncology in 2017 showed significantly improved disease-free survival, breast cancer–free interval, and distant recurrence–free interval in early stage breast cancer patients randomized to cholesterol-lowering medication vs. those who did not receive cholesterol-lowering medication.
The 2017 study prompted the creation of the MASTER study, a randomized, multicenter, double-blind, placebo-controlled trial comparing standard adjuvant therapy plus placebo to standard adjuvant therapy plus atorvastatin in patients with early breast cancer (NCT04601116), Mr. Harborg said. The MASTER trial is currently recruiting patients in Denmark.
How Was the Current Study Designed?
To provide preliminary analysis, Mr. Harborg and colleagues used an emulation trial design based on electronic health care data from 110,160 females with a diagnosis of stage I, II, or III breast cancer who were part of the Danish Breast Cancer Group, a national clinical registry in Denmark, between 2000 and 2020.
As defined in the European Journal of Epidemiology in 2017, target trial emulation involves application of randomized trial designs to observational data with the goal of improving the quality of observational epidemiology when a comparator trial is not yet available.
The researchers created a cohort of patients based on electronic health care data to simulate a target trial of the use of atorvastatin after breast cancer diagnosis. Patients were randomized to one of two treatment strategies: starting to use statins within 36 months of diagnosis, or not using statins. The primary outcome was death from breast cancer. The follow-up for the MASTER study starts with inclusion and ends with death, emigration from Denmark, end of clinical follow-up, or 10 years of follow-up (whichever comes first); the follow-up was the same in the current study.
The researchers calculated hazard ratios (HR) of breast cancer mortality in statin users vs. non–statin users and used a technique known as inverse-probability of censoring-weighting (IPCW) to estimate the effects of statin use based on prognostic factors.
What Did the Results Show?
The results favored statin use for improved survival in early breast cancer patients, Mr. Harborg said. Overall, the hazard ratio for breast cancer mortality was 0.96 in statin users compared with non–statin users, and was similar in both a Cox regression analysis (HR 0.81), and in a 10-year landmark analysis (HR 0.86).
The difference in mortality between statin and non–statin users was even stronger in patients who were receiving adjuvant chemotherapy (HR 0.94, 0.64, and 0.76 on the IPCW, Cox, and landmark analyses, respectively).
The results were in line with previous reports of statins’ effect on breast cancer survival, Mr. Harborg said in an interview.
“We believe the results encourage the continuous effort of the currently enrolling MASTER trial,” he said.
The results also suggest that deprescribing statins at the time of breast cancer diagnosis is not recommended, and that statin treatment can safely be prescribed to breast cancer patients with increased cardiovascular disease risk and/or dyslipidemia, Mr. Harborg said in the interview.
What Is the Takeaway Message for Clinical Practice?
“The clinical takeaway from our study is that statin use is associated with reduced risk of dying from breast cancer, but that it is not possible to determine the true effect of statins on breast cancer survival without a randomized, placebo-controlled trial,” Mr. Harborg told this publication. “Statins are inexpensive and well-tolerated drugs and may have a beneficial effect in terms of survival for breast cancer patients. However, with the current level of evidence [because the MASTER study is ongoing], we still cannot recommend that oncologists prescribe statins to prevent mortality from breast cancer,” he said.
What Are the Next Steps for Research?
The findings were limited by the study design, and real-world data are needed, Dr. Harborg said. Other limitations include the presence of residual bias, and the use of data based on prescription codes, but these were not considered to have an effect on the main conclusion of the study, Mr. Harborg said in the interview.
However, the results suggest that the addition of statins may improve outcomes for early breast cancer patients, especially when used with chemotherapy, and support the value of the ongoing MASTER study, he concluded.
Ultimately, the MASTER study will provide a more definitive answer to the question of whether statins should be added to the adjuvant treatment regimen of breast cancer to improve breast cancer outcomes, he said.
What Do Clinicians Think of the Study?
The current study is timely and highlights the need for phase 3 trials to examine the potential of statin use for breast cancer outcomes, Malinda T. West, MD, a medical oncologist and breast oncologist at the University of Wisconsin Carbone Cancer Center, Madison, said in an interview.
Questions for future research include whether statins can be used in combination with adjuvant abemaciclib if indicated, or how to best sequence these agents, said Dr. West, who was not involved in the study. Other questions raised by the current study include whether other cholesterol-lowering agents have a potential adjuvant benefit in reducing breast cancer recurrent and/or mortality, and whether the addition of statins would benefit subgroups such as HER2+ and triple negative breast cancer, she said.
“I was not surprised to see another study reporting benefit with statins and reduced risk of breast cancer recurrence and/or mortality, but I think the larger question is defining the subgroups who benefit the most, and identifying predictors for benefit or resistance,” Dr. West said in an interview.
Previous studies have shown that cholesterol elevation, specifically LDL levels, can be linked to increased tumor growth in breast cancer, so the lower mortality risk associated with lipid-lowering therapies in the current study was consistent, Peyton L. Reves, MD, a hematology/oncology fellow, also at the University of Wisconsin, said in an interview. In practice, data from the current study and previous research could be especially useful for patients with elevated LDL levels, said Dr. Reves, who was not involved in the study.
“These results could impact clinical practice in many ways, including leading to routine cholesterol monitoring in breast cancer patients on adjuvant therapy as well as the addition of lipid-lowering therapy with statins in these patients,” Dr. Reves said.
The findings showing particular benefit for patients on adjuvant chemotherapy highlight the need for more research on this specific population and the effect of statins on overall breast cancer mortality, to explore the extent to which the results of the current study were driven by the benefit seen in patients receiving adjuvant chemotherapy, Dr. Reves said.
The study was supported by Director Michael Hermann Nielsen’s Memorial Grant, Manufacturer Einar Willumsen’s Memorial Grant, Astrid Thaysen’s Grant for Medical Basic Research, Eva and Henry Fraenkel’s Memorial Fund, and the Novo Nordisk Foundation.
The researchers had no financial conflicts to disclose. Dr. West and Dr. Reves had no financial conflicts to disclose.
Previous research examining the association between cholesterol and breast cancer metabolism suggests that cholesterol-lowering medications such as statins may improve outcomes in breast cancer patients, Sixten Harborg, a medical student and PhD student at Aarhus University, Denmark, said in a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
In addition, cardiovascular-related death is the second most common cause of death for breast cancer survivors, and given the survival rates in early breast cancer, there is a demand for cardioprotective initiatives and maintenance of cardioprotective drugs after diagnosis, he said in an interview.
What Is Known About Statins and Breast Cancer?
Statins are the most common drugs used to lower cholesterol and may deprive tumor cells of the cholesterol needed for cell membrane synthesis, Mr. Harborg said in his presentation.
Data from a randomized trial published in the Journal of Clinical Oncology in 2017 showed significantly improved disease-free survival, breast cancer–free interval, and distant recurrence–free interval in early stage breast cancer patients randomized to cholesterol-lowering medication vs. those who did not receive cholesterol-lowering medication.
The 2017 study prompted the creation of the MASTER study, a randomized, multicenter, double-blind, placebo-controlled trial comparing standard adjuvant therapy plus placebo to standard adjuvant therapy plus atorvastatin in patients with early breast cancer (NCT04601116), Mr. Harborg said. The MASTER trial is currently recruiting patients in Denmark.
How Was the Current Study Designed?
To provide preliminary analysis, Mr. Harborg and colleagues used an emulation trial design based on electronic health care data from 110,160 females with a diagnosis of stage I, II, or III breast cancer who were part of the Danish Breast Cancer Group, a national clinical registry in Denmark, between 2000 and 2020.
As defined in the European Journal of Epidemiology in 2017, target trial emulation involves application of randomized trial designs to observational data with the goal of improving the quality of observational epidemiology when a comparator trial is not yet available.
The researchers created a cohort of patients based on electronic health care data to simulate a target trial of the use of atorvastatin after breast cancer diagnosis. Patients were randomized to one of two treatment strategies: starting to use statins within 36 months of diagnosis, or not using statins. The primary outcome was death from breast cancer. The follow-up for the MASTER study starts with inclusion and ends with death, emigration from Denmark, end of clinical follow-up, or 10 years of follow-up (whichever comes first); the follow-up was the same in the current study.
The researchers calculated hazard ratios (HR) of breast cancer mortality in statin users vs. non–statin users and used a technique known as inverse-probability of censoring-weighting (IPCW) to estimate the effects of statin use based on prognostic factors.
What Did the Results Show?
The results favored statin use for improved survival in early breast cancer patients, Mr. Harborg said. Overall, the hazard ratio for breast cancer mortality was 0.96 in statin users compared with non–statin users, and was similar in both a Cox regression analysis (HR 0.81), and in a 10-year landmark analysis (HR 0.86).
The difference in mortality between statin and non–statin users was even stronger in patients who were receiving adjuvant chemotherapy (HR 0.94, 0.64, and 0.76 on the IPCW, Cox, and landmark analyses, respectively).
The results were in line with previous reports of statins’ effect on breast cancer survival, Mr. Harborg said in an interview.
“We believe the results encourage the continuous effort of the currently enrolling MASTER trial,” he said.
The results also suggest that deprescribing statins at the time of breast cancer diagnosis is not recommended, and that statin treatment can safely be prescribed to breast cancer patients with increased cardiovascular disease risk and/or dyslipidemia, Mr. Harborg said in the interview.
What Is the Takeaway Message for Clinical Practice?
“The clinical takeaway from our study is that statin use is associated with reduced risk of dying from breast cancer, but that it is not possible to determine the true effect of statins on breast cancer survival without a randomized, placebo-controlled trial,” Mr. Harborg told this publication. “Statins are inexpensive and well-tolerated drugs and may have a beneficial effect in terms of survival for breast cancer patients. However, with the current level of evidence [because the MASTER study is ongoing], we still cannot recommend that oncologists prescribe statins to prevent mortality from breast cancer,” he said.
What Are the Next Steps for Research?
The findings were limited by the study design, and real-world data are needed, Dr. Harborg said. Other limitations include the presence of residual bias, and the use of data based on prescription codes, but these were not considered to have an effect on the main conclusion of the study, Mr. Harborg said in the interview.
However, the results suggest that the addition of statins may improve outcomes for early breast cancer patients, especially when used with chemotherapy, and support the value of the ongoing MASTER study, he concluded.
Ultimately, the MASTER study will provide a more definitive answer to the question of whether statins should be added to the adjuvant treatment regimen of breast cancer to improve breast cancer outcomes, he said.
What Do Clinicians Think of the Study?
The current study is timely and highlights the need for phase 3 trials to examine the potential of statin use for breast cancer outcomes, Malinda T. West, MD, a medical oncologist and breast oncologist at the University of Wisconsin Carbone Cancer Center, Madison, said in an interview.
Questions for future research include whether statins can be used in combination with adjuvant abemaciclib if indicated, or how to best sequence these agents, said Dr. West, who was not involved in the study. Other questions raised by the current study include whether other cholesterol-lowering agents have a potential adjuvant benefit in reducing breast cancer recurrent and/or mortality, and whether the addition of statins would benefit subgroups such as HER2+ and triple negative breast cancer, she said.
“I was not surprised to see another study reporting benefit with statins and reduced risk of breast cancer recurrence and/or mortality, but I think the larger question is defining the subgroups who benefit the most, and identifying predictors for benefit or resistance,” Dr. West said in an interview.
Previous studies have shown that cholesterol elevation, specifically LDL levels, can be linked to increased tumor growth in breast cancer, so the lower mortality risk associated with lipid-lowering therapies in the current study was consistent, Peyton L. Reves, MD, a hematology/oncology fellow, also at the University of Wisconsin, said in an interview. In practice, data from the current study and previous research could be especially useful for patients with elevated LDL levels, said Dr. Reves, who was not involved in the study.
“These results could impact clinical practice in many ways, including leading to routine cholesterol monitoring in breast cancer patients on adjuvant therapy as well as the addition of lipid-lowering therapy with statins in these patients,” Dr. Reves said.
The findings showing particular benefit for patients on adjuvant chemotherapy highlight the need for more research on this specific population and the effect of statins on overall breast cancer mortality, to explore the extent to which the results of the current study were driven by the benefit seen in patients receiving adjuvant chemotherapy, Dr. Reves said.
The study was supported by Director Michael Hermann Nielsen’s Memorial Grant, Manufacturer Einar Willumsen’s Memorial Grant, Astrid Thaysen’s Grant for Medical Basic Research, Eva and Henry Fraenkel’s Memorial Fund, and the Novo Nordisk Foundation.
The researchers had no financial conflicts to disclose. Dr. West and Dr. Reves had no financial conflicts to disclose.
Previous research examining the association between cholesterol and breast cancer metabolism suggests that cholesterol-lowering medications such as statins may improve outcomes in breast cancer patients, Sixten Harborg, a medical student and PhD student at Aarhus University, Denmark, said in a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
In addition, cardiovascular-related death is the second most common cause of death for breast cancer survivors, and given the survival rates in early breast cancer, there is a demand for cardioprotective initiatives and maintenance of cardioprotective drugs after diagnosis, he said in an interview.
What Is Known About Statins and Breast Cancer?
Statins are the most common drugs used to lower cholesterol and may deprive tumor cells of the cholesterol needed for cell membrane synthesis, Mr. Harborg said in his presentation.
Data from a randomized trial published in the Journal of Clinical Oncology in 2017 showed significantly improved disease-free survival, breast cancer–free interval, and distant recurrence–free interval in early stage breast cancer patients randomized to cholesterol-lowering medication vs. those who did not receive cholesterol-lowering medication.
The 2017 study prompted the creation of the MASTER study, a randomized, multicenter, double-blind, placebo-controlled trial comparing standard adjuvant therapy plus placebo to standard adjuvant therapy plus atorvastatin in patients with early breast cancer (NCT04601116), Mr. Harborg said. The MASTER trial is currently recruiting patients in Denmark.
How Was the Current Study Designed?
To provide preliminary analysis, Mr. Harborg and colleagues used an emulation trial design based on electronic health care data from 110,160 females with a diagnosis of stage I, II, or III breast cancer who were part of the Danish Breast Cancer Group, a national clinical registry in Denmark, between 2000 and 2020.
As defined in the European Journal of Epidemiology in 2017, target trial emulation involves application of randomized trial designs to observational data with the goal of improving the quality of observational epidemiology when a comparator trial is not yet available.
The researchers created a cohort of patients based on electronic health care data to simulate a target trial of the use of atorvastatin after breast cancer diagnosis. Patients were randomized to one of two treatment strategies: starting to use statins within 36 months of diagnosis, or not using statins. The primary outcome was death from breast cancer. The follow-up for the MASTER study starts with inclusion and ends with death, emigration from Denmark, end of clinical follow-up, or 10 years of follow-up (whichever comes first); the follow-up was the same in the current study.
The researchers calculated hazard ratios (HR) of breast cancer mortality in statin users vs. non–statin users and used a technique known as inverse-probability of censoring-weighting (IPCW) to estimate the effects of statin use based on prognostic factors.
What Did the Results Show?
The results favored statin use for improved survival in early breast cancer patients, Mr. Harborg said. Overall, the hazard ratio for breast cancer mortality was 0.96 in statin users compared with non–statin users, and was similar in both a Cox regression analysis (HR 0.81), and in a 10-year landmark analysis (HR 0.86).
The difference in mortality between statin and non–statin users was even stronger in patients who were receiving adjuvant chemotherapy (HR 0.94, 0.64, and 0.76 on the IPCW, Cox, and landmark analyses, respectively).
The results were in line with previous reports of statins’ effect on breast cancer survival, Mr. Harborg said in an interview.
“We believe the results encourage the continuous effort of the currently enrolling MASTER trial,” he said.
The results also suggest that deprescribing statins at the time of breast cancer diagnosis is not recommended, and that statin treatment can safely be prescribed to breast cancer patients with increased cardiovascular disease risk and/or dyslipidemia, Mr. Harborg said in the interview.
What Is the Takeaway Message for Clinical Practice?
“The clinical takeaway from our study is that statin use is associated with reduced risk of dying from breast cancer, but that it is not possible to determine the true effect of statins on breast cancer survival without a randomized, placebo-controlled trial,” Mr. Harborg told this publication. “Statins are inexpensive and well-tolerated drugs and may have a beneficial effect in terms of survival for breast cancer patients. However, with the current level of evidence [because the MASTER study is ongoing], we still cannot recommend that oncologists prescribe statins to prevent mortality from breast cancer,” he said.
What Are the Next Steps for Research?
The findings were limited by the study design, and real-world data are needed, Dr. Harborg said. Other limitations include the presence of residual bias, and the use of data based on prescription codes, but these were not considered to have an effect on the main conclusion of the study, Mr. Harborg said in the interview.
However, the results suggest that the addition of statins may improve outcomes for early breast cancer patients, especially when used with chemotherapy, and support the value of the ongoing MASTER study, he concluded.
Ultimately, the MASTER study will provide a more definitive answer to the question of whether statins should be added to the adjuvant treatment regimen of breast cancer to improve breast cancer outcomes, he said.
What Do Clinicians Think of the Study?
The current study is timely and highlights the need for phase 3 trials to examine the potential of statin use for breast cancer outcomes, Malinda T. West, MD, a medical oncologist and breast oncologist at the University of Wisconsin Carbone Cancer Center, Madison, said in an interview.
Questions for future research include whether statins can be used in combination with adjuvant abemaciclib if indicated, or how to best sequence these agents, said Dr. West, who was not involved in the study. Other questions raised by the current study include whether other cholesterol-lowering agents have a potential adjuvant benefit in reducing breast cancer recurrent and/or mortality, and whether the addition of statins would benefit subgroups such as HER2+ and triple negative breast cancer, she said.
“I was not surprised to see another study reporting benefit with statins and reduced risk of breast cancer recurrence and/or mortality, but I think the larger question is defining the subgroups who benefit the most, and identifying predictors for benefit or resistance,” Dr. West said in an interview.
Previous studies have shown that cholesterol elevation, specifically LDL levels, can be linked to increased tumor growth in breast cancer, so the lower mortality risk associated with lipid-lowering therapies in the current study was consistent, Peyton L. Reves, MD, a hematology/oncology fellow, also at the University of Wisconsin, said in an interview. In practice, data from the current study and previous research could be especially useful for patients with elevated LDL levels, said Dr. Reves, who was not involved in the study.
“These results could impact clinical practice in many ways, including leading to routine cholesterol monitoring in breast cancer patients on adjuvant therapy as well as the addition of lipid-lowering therapy with statins in these patients,” Dr. Reves said.
The findings showing particular benefit for patients on adjuvant chemotherapy highlight the need for more research on this specific population and the effect of statins on overall breast cancer mortality, to explore the extent to which the results of the current study were driven by the benefit seen in patients receiving adjuvant chemotherapy, Dr. Reves said.
The study was supported by Director Michael Hermann Nielsen’s Memorial Grant, Manufacturer Einar Willumsen’s Memorial Grant, Astrid Thaysen’s Grant for Medical Basic Research, Eva and Henry Fraenkel’s Memorial Fund, and the Novo Nordisk Foundation.
The researchers had no financial conflicts to disclose. Dr. West and Dr. Reves had no financial conflicts to disclose.
FROM ESMO BREAST CANCER 2024
New Immunotherapy Combo Shows Promise for Triple-Negative Breast Cancer
MORPHEUS-pan BC (NCT03424005) is evaluating multiple treatment combinations in patients with locally advanced or metastatic TNBC.
The trial’s interim clinical data was presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
Rationale for Combining Antibody-Drug Conjugates with Immunotherapy
Peter Schmid, MD, PhD, professor at the Centre for Experimental Cancer Medicine in London, England, presented interim findings from one study arm of MORPHEUS-pan BC at the meeting. The arm consisted of patients with TNBC who were treated with a combination of atezolizumab, a PD-L1 inhibitor, and sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein commonly expressed in TNBC.
TNBC is one of the most challenging subtypes of breast cancer to treat because of its aggressive characteristics and innate resistance to hormonal therapy and HER2-targeted treatments. However, the recent approval of immunotherapy for TNBC has provided renewed hope for patients, according to Dr. Schmid.
Atezolizumab, in combination with nab-paclitaxel, has already been approved as a first-line treatment for PD-L1–positive, unresectable locally advanced or metastatic TNBC; however, not all patients respond to this combination treatment. Sacituzumab govitecan is approved for second-line and subsequent-line treatment of metastatic TNBC.
“Cancer immunotherapy in combination with chemotherapy has transformed the TNBC treatment landscape, but new combinations are needed to further improve survival outcomes,” Dr. Schmid said during his presentation. “We hoped that combining immunotherapy with an antibody-drug conjugate would not only improve safety but also increase efficacy through enhanced immune activation.”
Study Design
The MORPHEUS-pan BC trial enrolled patients with previously untreated, PD-L1–positive, inoperable, locally advanced or metastatic TNBC. Patients were randomized to receive experimental treatment consisting of atezolizumab plus the antibody-drug conjugate sacituzumab govitecan. Patients in the second arm received a control regimen of atezolizumab plus nab-paclitaxel chemotherapy.
“The control regimen is part of the current standard of care for patients with PD-L1–positive TNBC,” Dr. Schmid explained in his presentation. As of the data cut-off, 11 patients were enrolled in the control arm and 31 in the atezolizumab plus sacituzumab govitecan arm.
During the discussion session after his talk, Dr. Schmid commented on the use of PD-L1 expression to select patients for enrollment, acknowledging that PD-L1 is not the best biomarker.
“Its expression is very dynamic and can change rapidly,” he said. He added, however, that it is currently the most suitable biomarker for patient selection for treatment with anti–PD-1/PD-L1 agents.
Sara M. Tolaney, MD, MPH, added that, because patients were selected based on PD-L1 expression, it is unclear whether this combination therapy would show anti-tumor activity in patients with PD-L1–negative tumors. Dr. Tolaney, a medical oncologist at the Dana-Farber Cancer Institute who was not involved in the study, served as a discussant, providing her expert opinion on the findings presented by Dr. Schmid.
Promising Anti-tumor Activity
The combination of atezolizumab and sacituzumab govitecan demonstrated promising anti-tumor activity as initial treatment for this patient population. The interim analysis at 18 weeks showed an objective response rate of 76.7% (95% CI, 57.7-90.1; n = 23, including five complete responses) in the atezolizumab plus sacituzumab govitecan arm, versus 66.7% (95% CI, 29.9-92.5; n = 6, all of which were partial responses) in the control arm.
“The 66% response rate in the control arm aligns with what we see in historical data from patients treated with immunotherapy plus chemotherapy,” noted Dr. Schmid during his talk.
The clinical benefit rate, which includes complete and partial responses as well as stable disease, was also encouraging at 83.3% (95% CI, 65.3-94.4) with the dual immunotherapy regimen versus 66.7% (95% CI, 29.9-92.5) with standard therapy.
Commenting on the potential mechanisms of the synergistic effect of this combination therapy, Dr. Tolaney said, “In addition to delivering chemotherapy payloads to cancer cells, antibody-drug conjugates can lead to dendritic cell activation, T-cell activation, and immune cell infiltration.”
She added that antibody-drug conjugates can cause Fc activation in NK cells, thereby enhancing antibody-dependent cytotoxicity.
Encouraging survival trends
Interim survival data showed trends favoring atezolizumab plus sacituzumab govitecan over the control arm of atezolizumab plus nab-paclitaxel chemotherapy. The median progression-free survival (PFS) was 12.2 months (95% CI, 7.4-not estimable) in the immunotherapy combination group versus 5.9 months (95% CI, 4.1-8.7) in the control group, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.70). The overall survival data are still immature.
During the discussion session, Dr. Schmid cautioned that, although the benefit of this combination therapy in terms of PFS seems promising, the validity of the hazard ratio is limited because of the small cohort size. He added, “The survival data is still immature, and longer follow-up is needed.”
These encouraging response and PFS rates need to be confirmed in larger studies of this immunotherapy combination as a potential new first-line standard for PD-L1–positive TNBC, according to Dr. Schmid.
Relationship between biomarker expression and response
The MORPHEUS-pan BC trial enrolled only patients with PD-L1–positive tumors at baseline, defined as PD-L1 expression in at least 1% of immune cells infiltrating the tumor. Tumors at baseline were also tested for Trop-2 expression, CD8 immune phenotype, and stromal tumor-infiltrating lymphocytes (TILs).
“We wanted to get an idea of whether these biomarkers are associated with treatment response,” Dr. Schmid explained during his talk.
Although the benefit of sacituzumab govitecan treatment was observed across all Trop-2 expression levels, preliminary analyses suggest that high Trop-2 expression, CD8 immune phenotype, and stromal TILs may be associated with response to atezolizumab plus sacituzumab govitecan. However, Dr. Schmid noted that validation of these associations in larger cohorts is required.
Safety of combination treatment
The side effect profile of atezolizumab plus sacituzumab govitecan appeared consistent with that expected from the two individual drugs, with no new toxicity signals.
All patients in both treatment arms experienced at least one adverse event; however, there were no fatal adverse events. Grade 3-4 adverse events were more common in the experimental arm (70.0%) than in the control arm (44.4%), while serious adverse events were more common in the control group (44.4% versus 23.3%). Immune-related adverse events were considerably more common in the atezolizumab plus sacituzumab govitecan group than in the control group (80.0% versus 55.6%).
The most common adverse events in patients treated with atezolizumab plus sacituzumab govitecan were nausea, alopecia, diarrhea, and neutropenia. Dr. Schmid emphasized in his presentation that this toxicity profile was dominated by adverse events that are common in patients treated with chemotherapy.
“These safety data are significant as they suggest that the combination therapy does not introduce additional risks beyond those already associated with each drug,” he added.
Looking Ahead
Dr. Tolaney highlighted that the cohort size of this study was small and the follow-up time was insufficient to draw conclusions about survival outcomes. Larger studies with long-term follow-up are needed to confirm the efficacy of first-line atezolizumab plus sacituzumab govitecan, she said.
“While this was a small study, the response data is very intriguing, with 17% of patients experiencing complete responses. The PFS data are also impressive, and there seems to be an interesting trend towards better response in patients with high Trop-2 expression and those with high levels of stromal TILs,” she added.
Dr. Tolaney also noted that the response rates and PFS data presented are similar to those of one of the treatment arms in the BEGONIA trial (NCT03742102), which investigated different combinations of immunotherapy in patients with metastatic TNBC. Like MORPHEUS-pan BC (NCT03424005), this study evaluated the efficacy of a different antibody-drug conjugate with chemotherapy. Patients in the study arm of the BEGONIA trial she was referring to received durvalumab (an anti-PD-L1 agent) and datopotamab deruxtecan (an antibody-drug conjugate).
Dr. Schmid said that biomarker analyses are ongoing to assess whether there is a correlation between Trop-2 expression levels and the benefits of sacituzumab govitecan. Studies are also needed to determine whether this combination can improve pathologic complete response rates in early-stage TNBC.
Dr. Tolaney echoed the importance of evaluating the efficacy of antibody-drug conjugates plus immune checkpoint inhibitors in different settings, including patients with PD-L1–negative or immunologically cold tumors and those with early-stage disease. “Ultimately, we want this combination treatment to move forward to early-stage TNBC to see if we could cure more patients,” she said, during the discussion.
Dr. Schmid reported financial relationships with Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (consulting or advisory roles); Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (honoraria); and AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas, and Medivation (research funding). Dr. Tolaney reported financial relationships with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., Beyond Spring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, and Jazz Pharmaceuticals (consulting or advisory roles); Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics (research funding).
MORPHEUS-pan BC (NCT03424005) is evaluating multiple treatment combinations in patients with locally advanced or metastatic TNBC.
The trial’s interim clinical data was presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
Rationale for Combining Antibody-Drug Conjugates with Immunotherapy
Peter Schmid, MD, PhD, professor at the Centre for Experimental Cancer Medicine in London, England, presented interim findings from one study arm of MORPHEUS-pan BC at the meeting. The arm consisted of patients with TNBC who were treated with a combination of atezolizumab, a PD-L1 inhibitor, and sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein commonly expressed in TNBC.
TNBC is one of the most challenging subtypes of breast cancer to treat because of its aggressive characteristics and innate resistance to hormonal therapy and HER2-targeted treatments. However, the recent approval of immunotherapy for TNBC has provided renewed hope for patients, according to Dr. Schmid.
Atezolizumab, in combination with nab-paclitaxel, has already been approved as a first-line treatment for PD-L1–positive, unresectable locally advanced or metastatic TNBC; however, not all patients respond to this combination treatment. Sacituzumab govitecan is approved for second-line and subsequent-line treatment of metastatic TNBC.
“Cancer immunotherapy in combination with chemotherapy has transformed the TNBC treatment landscape, but new combinations are needed to further improve survival outcomes,” Dr. Schmid said during his presentation. “We hoped that combining immunotherapy with an antibody-drug conjugate would not only improve safety but also increase efficacy through enhanced immune activation.”
Study Design
The MORPHEUS-pan BC trial enrolled patients with previously untreated, PD-L1–positive, inoperable, locally advanced or metastatic TNBC. Patients were randomized to receive experimental treatment consisting of atezolizumab plus the antibody-drug conjugate sacituzumab govitecan. Patients in the second arm received a control regimen of atezolizumab plus nab-paclitaxel chemotherapy.
“The control regimen is part of the current standard of care for patients with PD-L1–positive TNBC,” Dr. Schmid explained in his presentation. As of the data cut-off, 11 patients were enrolled in the control arm and 31 in the atezolizumab plus sacituzumab govitecan arm.
During the discussion session after his talk, Dr. Schmid commented on the use of PD-L1 expression to select patients for enrollment, acknowledging that PD-L1 is not the best biomarker.
“Its expression is very dynamic and can change rapidly,” he said. He added, however, that it is currently the most suitable biomarker for patient selection for treatment with anti–PD-1/PD-L1 agents.
Sara M. Tolaney, MD, MPH, added that, because patients were selected based on PD-L1 expression, it is unclear whether this combination therapy would show anti-tumor activity in patients with PD-L1–negative tumors. Dr. Tolaney, a medical oncologist at the Dana-Farber Cancer Institute who was not involved in the study, served as a discussant, providing her expert opinion on the findings presented by Dr. Schmid.
Promising Anti-tumor Activity
The combination of atezolizumab and sacituzumab govitecan demonstrated promising anti-tumor activity as initial treatment for this patient population. The interim analysis at 18 weeks showed an objective response rate of 76.7% (95% CI, 57.7-90.1; n = 23, including five complete responses) in the atezolizumab plus sacituzumab govitecan arm, versus 66.7% (95% CI, 29.9-92.5; n = 6, all of which were partial responses) in the control arm.
“The 66% response rate in the control arm aligns with what we see in historical data from patients treated with immunotherapy plus chemotherapy,” noted Dr. Schmid during his talk.
The clinical benefit rate, which includes complete and partial responses as well as stable disease, was also encouraging at 83.3% (95% CI, 65.3-94.4) with the dual immunotherapy regimen versus 66.7% (95% CI, 29.9-92.5) with standard therapy.
Commenting on the potential mechanisms of the synergistic effect of this combination therapy, Dr. Tolaney said, “In addition to delivering chemotherapy payloads to cancer cells, antibody-drug conjugates can lead to dendritic cell activation, T-cell activation, and immune cell infiltration.”
She added that antibody-drug conjugates can cause Fc activation in NK cells, thereby enhancing antibody-dependent cytotoxicity.
Encouraging survival trends
Interim survival data showed trends favoring atezolizumab plus sacituzumab govitecan over the control arm of atezolizumab plus nab-paclitaxel chemotherapy. The median progression-free survival (PFS) was 12.2 months (95% CI, 7.4-not estimable) in the immunotherapy combination group versus 5.9 months (95% CI, 4.1-8.7) in the control group, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.70). The overall survival data are still immature.
During the discussion session, Dr. Schmid cautioned that, although the benefit of this combination therapy in terms of PFS seems promising, the validity of the hazard ratio is limited because of the small cohort size. He added, “The survival data is still immature, and longer follow-up is needed.”
These encouraging response and PFS rates need to be confirmed in larger studies of this immunotherapy combination as a potential new first-line standard for PD-L1–positive TNBC, according to Dr. Schmid.
Relationship between biomarker expression and response
The MORPHEUS-pan BC trial enrolled only patients with PD-L1–positive tumors at baseline, defined as PD-L1 expression in at least 1% of immune cells infiltrating the tumor. Tumors at baseline were also tested for Trop-2 expression, CD8 immune phenotype, and stromal tumor-infiltrating lymphocytes (TILs).
“We wanted to get an idea of whether these biomarkers are associated with treatment response,” Dr. Schmid explained during his talk.
Although the benefit of sacituzumab govitecan treatment was observed across all Trop-2 expression levels, preliminary analyses suggest that high Trop-2 expression, CD8 immune phenotype, and stromal TILs may be associated with response to atezolizumab plus sacituzumab govitecan. However, Dr. Schmid noted that validation of these associations in larger cohorts is required.
Safety of combination treatment
The side effect profile of atezolizumab plus sacituzumab govitecan appeared consistent with that expected from the two individual drugs, with no new toxicity signals.
All patients in both treatment arms experienced at least one adverse event; however, there were no fatal adverse events. Grade 3-4 adverse events were more common in the experimental arm (70.0%) than in the control arm (44.4%), while serious adverse events were more common in the control group (44.4% versus 23.3%). Immune-related adverse events were considerably more common in the atezolizumab plus sacituzumab govitecan group than in the control group (80.0% versus 55.6%).
The most common adverse events in patients treated with atezolizumab plus sacituzumab govitecan were nausea, alopecia, diarrhea, and neutropenia. Dr. Schmid emphasized in his presentation that this toxicity profile was dominated by adverse events that are common in patients treated with chemotherapy.
“These safety data are significant as they suggest that the combination therapy does not introduce additional risks beyond those already associated with each drug,” he added.
Looking Ahead
Dr. Tolaney highlighted that the cohort size of this study was small and the follow-up time was insufficient to draw conclusions about survival outcomes. Larger studies with long-term follow-up are needed to confirm the efficacy of first-line atezolizumab plus sacituzumab govitecan, she said.
“While this was a small study, the response data is very intriguing, with 17% of patients experiencing complete responses. The PFS data are also impressive, and there seems to be an interesting trend towards better response in patients with high Trop-2 expression and those with high levels of stromal TILs,” she added.
Dr. Tolaney also noted that the response rates and PFS data presented are similar to those of one of the treatment arms in the BEGONIA trial (NCT03742102), which investigated different combinations of immunotherapy in patients with metastatic TNBC. Like MORPHEUS-pan BC (NCT03424005), this study evaluated the efficacy of a different antibody-drug conjugate with chemotherapy. Patients in the study arm of the BEGONIA trial she was referring to received durvalumab (an anti-PD-L1 agent) and datopotamab deruxtecan (an antibody-drug conjugate).
Dr. Schmid said that biomarker analyses are ongoing to assess whether there is a correlation between Trop-2 expression levels and the benefits of sacituzumab govitecan. Studies are also needed to determine whether this combination can improve pathologic complete response rates in early-stage TNBC.
Dr. Tolaney echoed the importance of evaluating the efficacy of antibody-drug conjugates plus immune checkpoint inhibitors in different settings, including patients with PD-L1–negative or immunologically cold tumors and those with early-stage disease. “Ultimately, we want this combination treatment to move forward to early-stage TNBC to see if we could cure more patients,” she said, during the discussion.
Dr. Schmid reported financial relationships with Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (consulting or advisory roles); Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (honoraria); and AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas, and Medivation (research funding). Dr. Tolaney reported financial relationships with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., Beyond Spring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, and Jazz Pharmaceuticals (consulting or advisory roles); Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics (research funding).
MORPHEUS-pan BC (NCT03424005) is evaluating multiple treatment combinations in patients with locally advanced or metastatic TNBC.
The trial’s interim clinical data was presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
Rationale for Combining Antibody-Drug Conjugates with Immunotherapy
Peter Schmid, MD, PhD, professor at the Centre for Experimental Cancer Medicine in London, England, presented interim findings from one study arm of MORPHEUS-pan BC at the meeting. The arm consisted of patients with TNBC who were treated with a combination of atezolizumab, a PD-L1 inhibitor, and sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein commonly expressed in TNBC.
TNBC is one of the most challenging subtypes of breast cancer to treat because of its aggressive characteristics and innate resistance to hormonal therapy and HER2-targeted treatments. However, the recent approval of immunotherapy for TNBC has provided renewed hope for patients, according to Dr. Schmid.
Atezolizumab, in combination with nab-paclitaxel, has already been approved as a first-line treatment for PD-L1–positive, unresectable locally advanced or metastatic TNBC; however, not all patients respond to this combination treatment. Sacituzumab govitecan is approved for second-line and subsequent-line treatment of metastatic TNBC.
“Cancer immunotherapy in combination with chemotherapy has transformed the TNBC treatment landscape, but new combinations are needed to further improve survival outcomes,” Dr. Schmid said during his presentation. “We hoped that combining immunotherapy with an antibody-drug conjugate would not only improve safety but also increase efficacy through enhanced immune activation.”
Study Design
The MORPHEUS-pan BC trial enrolled patients with previously untreated, PD-L1–positive, inoperable, locally advanced or metastatic TNBC. Patients were randomized to receive experimental treatment consisting of atezolizumab plus the antibody-drug conjugate sacituzumab govitecan. Patients in the second arm received a control regimen of atezolizumab plus nab-paclitaxel chemotherapy.
“The control regimen is part of the current standard of care for patients with PD-L1–positive TNBC,” Dr. Schmid explained in his presentation. As of the data cut-off, 11 patients were enrolled in the control arm and 31 in the atezolizumab plus sacituzumab govitecan arm.
During the discussion session after his talk, Dr. Schmid commented on the use of PD-L1 expression to select patients for enrollment, acknowledging that PD-L1 is not the best biomarker.
“Its expression is very dynamic and can change rapidly,” he said. He added, however, that it is currently the most suitable biomarker for patient selection for treatment with anti–PD-1/PD-L1 agents.
Sara M. Tolaney, MD, MPH, added that, because patients were selected based on PD-L1 expression, it is unclear whether this combination therapy would show anti-tumor activity in patients with PD-L1–negative tumors. Dr. Tolaney, a medical oncologist at the Dana-Farber Cancer Institute who was not involved in the study, served as a discussant, providing her expert opinion on the findings presented by Dr. Schmid.
Promising Anti-tumor Activity
The combination of atezolizumab and sacituzumab govitecan demonstrated promising anti-tumor activity as initial treatment for this patient population. The interim analysis at 18 weeks showed an objective response rate of 76.7% (95% CI, 57.7-90.1; n = 23, including five complete responses) in the atezolizumab plus sacituzumab govitecan arm, versus 66.7% (95% CI, 29.9-92.5; n = 6, all of which were partial responses) in the control arm.
“The 66% response rate in the control arm aligns with what we see in historical data from patients treated with immunotherapy plus chemotherapy,” noted Dr. Schmid during his talk.
The clinical benefit rate, which includes complete and partial responses as well as stable disease, was also encouraging at 83.3% (95% CI, 65.3-94.4) with the dual immunotherapy regimen versus 66.7% (95% CI, 29.9-92.5) with standard therapy.
Commenting on the potential mechanisms of the synergistic effect of this combination therapy, Dr. Tolaney said, “In addition to delivering chemotherapy payloads to cancer cells, antibody-drug conjugates can lead to dendritic cell activation, T-cell activation, and immune cell infiltration.”
She added that antibody-drug conjugates can cause Fc activation in NK cells, thereby enhancing antibody-dependent cytotoxicity.
Encouraging survival trends
Interim survival data showed trends favoring atezolizumab plus sacituzumab govitecan over the control arm of atezolizumab plus nab-paclitaxel chemotherapy. The median progression-free survival (PFS) was 12.2 months (95% CI, 7.4-not estimable) in the immunotherapy combination group versus 5.9 months (95% CI, 4.1-8.7) in the control group, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.70). The overall survival data are still immature.
During the discussion session, Dr. Schmid cautioned that, although the benefit of this combination therapy in terms of PFS seems promising, the validity of the hazard ratio is limited because of the small cohort size. He added, “The survival data is still immature, and longer follow-up is needed.”
These encouraging response and PFS rates need to be confirmed in larger studies of this immunotherapy combination as a potential new first-line standard for PD-L1–positive TNBC, according to Dr. Schmid.
Relationship between biomarker expression and response
The MORPHEUS-pan BC trial enrolled only patients with PD-L1–positive tumors at baseline, defined as PD-L1 expression in at least 1% of immune cells infiltrating the tumor. Tumors at baseline were also tested for Trop-2 expression, CD8 immune phenotype, and stromal tumor-infiltrating lymphocytes (TILs).
“We wanted to get an idea of whether these biomarkers are associated with treatment response,” Dr. Schmid explained during his talk.
Although the benefit of sacituzumab govitecan treatment was observed across all Trop-2 expression levels, preliminary analyses suggest that high Trop-2 expression, CD8 immune phenotype, and stromal TILs may be associated with response to atezolizumab plus sacituzumab govitecan. However, Dr. Schmid noted that validation of these associations in larger cohorts is required.
Safety of combination treatment
The side effect profile of atezolizumab plus sacituzumab govitecan appeared consistent with that expected from the two individual drugs, with no new toxicity signals.
All patients in both treatment arms experienced at least one adverse event; however, there were no fatal adverse events. Grade 3-4 adverse events were more common in the experimental arm (70.0%) than in the control arm (44.4%), while serious adverse events were more common in the control group (44.4% versus 23.3%). Immune-related adverse events were considerably more common in the atezolizumab plus sacituzumab govitecan group than in the control group (80.0% versus 55.6%).
The most common adverse events in patients treated with atezolizumab plus sacituzumab govitecan were nausea, alopecia, diarrhea, and neutropenia. Dr. Schmid emphasized in his presentation that this toxicity profile was dominated by adverse events that are common in patients treated with chemotherapy.
“These safety data are significant as they suggest that the combination therapy does not introduce additional risks beyond those already associated with each drug,” he added.
Looking Ahead
Dr. Tolaney highlighted that the cohort size of this study was small and the follow-up time was insufficient to draw conclusions about survival outcomes. Larger studies with long-term follow-up are needed to confirm the efficacy of first-line atezolizumab plus sacituzumab govitecan, she said.
“While this was a small study, the response data is very intriguing, with 17% of patients experiencing complete responses. The PFS data are also impressive, and there seems to be an interesting trend towards better response in patients with high Trop-2 expression and those with high levels of stromal TILs,” she added.
Dr. Tolaney also noted that the response rates and PFS data presented are similar to those of one of the treatment arms in the BEGONIA trial (NCT03742102), which investigated different combinations of immunotherapy in patients with metastatic TNBC. Like MORPHEUS-pan BC (NCT03424005), this study evaluated the efficacy of a different antibody-drug conjugate with chemotherapy. Patients in the study arm of the BEGONIA trial she was referring to received durvalumab (an anti-PD-L1 agent) and datopotamab deruxtecan (an antibody-drug conjugate).
Dr. Schmid said that biomarker analyses are ongoing to assess whether there is a correlation between Trop-2 expression levels and the benefits of sacituzumab govitecan. Studies are also needed to determine whether this combination can improve pathologic complete response rates in early-stage TNBC.
Dr. Tolaney echoed the importance of evaluating the efficacy of antibody-drug conjugates plus immune checkpoint inhibitors in different settings, including patients with PD-L1–negative or immunologically cold tumors and those with early-stage disease. “Ultimately, we want this combination treatment to move forward to early-stage TNBC to see if we could cure more patients,” she said, during the discussion.
Dr. Schmid reported financial relationships with Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (consulting or advisory roles); Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (honoraria); and AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas, and Medivation (research funding). Dr. Tolaney reported financial relationships with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., Beyond Spring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, and Jazz Pharmaceuticals (consulting or advisory roles); Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics (research funding).
FROM ESMO BREAST CANCER 2024
ART Safe for Breast Cancer Survivors with BRCA1/2 Mutations
For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However,
“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
Unmet Fertility Needs for Women With Breast Cancer
With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.
According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.
“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
Study Design and Patient Population
The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.
Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.
Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
No Increased Risks for Pregnancy and Fetal Outcomes
Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.
Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.
“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
No Adverse Effects on Breast Cancer Prognosis
At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).
“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.
Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.
“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
Clinical Implications and Future Work
According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.
“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”
During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.
“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.
She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”
Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”
Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).
For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However,
“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
Unmet Fertility Needs for Women With Breast Cancer
With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.
According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.
“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
Study Design and Patient Population
The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.
Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.
Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
No Increased Risks for Pregnancy and Fetal Outcomes
Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.
Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.
“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
No Adverse Effects on Breast Cancer Prognosis
At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).
“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.
Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.
“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
Clinical Implications and Future Work
According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.
“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”
During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.
“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.
She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”
Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”
Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).
For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However,
“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
Unmet Fertility Needs for Women With Breast Cancer
With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.
According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.
“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
Study Design and Patient Population
The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.
Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.
Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
No Increased Risks for Pregnancy and Fetal Outcomes
Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.
Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.
“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
No Adverse Effects on Breast Cancer Prognosis
At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).
“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.
Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.
“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
Clinical Implications and Future Work
According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.
“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”
During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.
“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.
She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”
Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”
Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).
FROM ESMO BREAST CANCER 2024
No Improvement in OS With Atezolizumab in Early Relapsing TNBC
Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
“These patients have a dismal prognosis and represent a high unmet need,” she added.
The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.
Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.
“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”
IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.
Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.
Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.
The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.
The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.
After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).
A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.
Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”
The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.
There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.
“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”
The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.
Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse.
This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.”
The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.
IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.
“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”
The study was sponsored by Hoffmann-La Roche.
Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.
A version of this article appeared on Medscape.com .
Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
“These patients have a dismal prognosis and represent a high unmet need,” she added.
The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.
Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.
“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”
IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.
Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.
Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.
The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.
The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.
After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).
A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.
Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”
The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.
There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.
“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”
The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.
Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse.
This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.”
The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.
IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.
“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”
The study was sponsored by Hoffmann-La Roche.
Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.
A version of this article appeared on Medscape.com .
Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
“These patients have a dismal prognosis and represent a high unmet need,” she added.
The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.
Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.
“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”
IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.
Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.
Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.
The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.
The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.
After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).
A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.
Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”
The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.
There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.
“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”
The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.
Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse.
This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.”
The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.
IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.
“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”
The study was sponsored by Hoffmann-La Roche.
Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.
A version of this article appeared on Medscape.com .
FROM ESMO BREAST CANCER 2024
Chatbots Seem More Empathetic Than Docs in Cancer Discussions
Large language models (LLM) such as ChatGPT have shown mixed results in the quality of their responses to consumer questions about cancer.
One recent study found AI chatbots to churn out incomplete, inaccurate, or even nonsensical cancer treatment recommendations, while another found them to generate largely accurate — if technical — responses to the most common cancer questions.
While researchers have seen success with purpose-built chatbots created to address patient concerns about specific cancers, the consensus to date has been that the generalized models like ChatGPT remain works in progress and that physicians should avoid pointing patients to them, for now.
Yet new findings suggest that these chatbots may do better than individual physicians, at least on some measures, when it comes to answering queries about cancer. For research published May 16 in JAMA Oncology (doi: 10.1001/jamaoncol.2024.0836), David Chen, a medical student at the University of Toronto, and his colleagues, isolated a random sample of 200 questions related to cancer care addressed to doctors on the public online forum Reddit. They then compared responses from oncologists with responses generated by three different AI chatbots. The blinded responses were rated for quality, readability, and empathy by six physicians, including oncologists and palliative and supportive care specialists.
Mr. Chen and colleagues’ research was modeled after a 2023 study that measured the quality of physician responses compared with chatbots for general medicine questions addressed to doctors on Reddit. That study found that the chatbots produced more empathetic-sounding answers, something Mr. Chen’s study also found. : quality, empathy, and readability.
Q&A With Author of New Research
Mr. Chen discussed his new study’s implications during an interview with this news organization.
Question: What is novel about this study?
Mr. Chen: We’ve seen many evaluations of chatbots that test for medical accuracy, but this study occurs in the domain of oncology care, where there are unique psychosocial and emotional considerations that are not precisely reflected in a general medicine setting. In effect, this study is putting these chatbots through a harder challenge.
Question: Why would chatbot responses seem more empathetic than those of physicians?
Mr. Chen: With the physician responses that we observed in our sample data set, we saw that there was very high variation of amount of apparent effort [in the physician responses]. Some physicians would put in a lot of time and effort, thinking through their response, and others wouldn’t do so as much. These chatbots don’t face fatigue the way humans do, or burnout. So they’re able to consistently provide responses with less variation in empathy.
Question: Do chatbots just seem empathetic because they are chattier?
Mr. Chen: We did think of verbosity as a potential confounder in this study. So we set a word count limit for the chatbot responses to keep it in the range of the physician responses. That way, verbosity was no longer a significant factor.
Question: How were quality and empathy measured by the reviewers?
Mr. Chen: For our study we used two teams of readers, each team composed of three physicians. In terms of the actual metrics we used, they were pilot metrics. There are no well-defined measurement scales or checklists that we could use to measure empathy. This is an emerging field of research. So we came up by consensus with our own set of ratings, and we feel that this is an area for the research to define a standardized set of guidelines.
Another novel aspect of this study is that we separated out different dimensions of quality and empathy. A quality response didn’t just mean it was medically accurate — quality also had to do with the focus and completeness of the response.
With empathy there are cognitive and emotional dimensions. Cognitive empathy uses critical thinking to understand the person’s emotions and thoughts and then adjusting a response to fit that. A patient may not want the best medically indicated treatment for their condition, because they want to preserve their quality of life. The chatbot may be able to adjust its recommendation with consideration of some of those humanistic elements that the patient is presenting with.
Emotional empathy is more about being supportive of the patient’s emotions by using expressions like ‘I understand where you’re coming from.’ or, ‘I can see how that makes you feel.’
Question: Why would physicians, not patients, be the best evaluators of empathy?
Mr. Chen: We’re actually very interested in evaluating patient ratings of empathy. We are conducting a follow-up study that evaluates patient ratings of empathy to the same set of chatbot and physician responses,to see if there are differences.
Question: Should cancer patients go ahead and consult chatbots?
Mr. Chen: Although we did observe increases in all of the metrics compared with physicians, this is a very specialized evaluation scenario where we’re using these Reddit questions and responses.
Naturally, we would need to do a trial, a head to head randomized comparison of physicians versus chatbots.
This pilot study does highlight the promising potential of these chatbots to suggest responses. But we can’t fully recommend that they should be used as standalone clinical tools without physicians.
This Q&A was edited for clarity.
Large language models (LLM) such as ChatGPT have shown mixed results in the quality of their responses to consumer questions about cancer.
One recent study found AI chatbots to churn out incomplete, inaccurate, or even nonsensical cancer treatment recommendations, while another found them to generate largely accurate — if technical — responses to the most common cancer questions.
While researchers have seen success with purpose-built chatbots created to address patient concerns about specific cancers, the consensus to date has been that the generalized models like ChatGPT remain works in progress and that physicians should avoid pointing patients to them, for now.
Yet new findings suggest that these chatbots may do better than individual physicians, at least on some measures, when it comes to answering queries about cancer. For research published May 16 in JAMA Oncology (doi: 10.1001/jamaoncol.2024.0836), David Chen, a medical student at the University of Toronto, and his colleagues, isolated a random sample of 200 questions related to cancer care addressed to doctors on the public online forum Reddit. They then compared responses from oncologists with responses generated by three different AI chatbots. The blinded responses were rated for quality, readability, and empathy by six physicians, including oncologists and palliative and supportive care specialists.
Mr. Chen and colleagues’ research was modeled after a 2023 study that measured the quality of physician responses compared with chatbots for general medicine questions addressed to doctors on Reddit. That study found that the chatbots produced more empathetic-sounding answers, something Mr. Chen’s study also found. : quality, empathy, and readability.
Q&A With Author of New Research
Mr. Chen discussed his new study’s implications during an interview with this news organization.
Question: What is novel about this study?
Mr. Chen: We’ve seen many evaluations of chatbots that test for medical accuracy, but this study occurs in the domain of oncology care, where there are unique psychosocial and emotional considerations that are not precisely reflected in a general medicine setting. In effect, this study is putting these chatbots through a harder challenge.
Question: Why would chatbot responses seem more empathetic than those of physicians?
Mr. Chen: With the physician responses that we observed in our sample data set, we saw that there was very high variation of amount of apparent effort [in the physician responses]. Some physicians would put in a lot of time and effort, thinking through their response, and others wouldn’t do so as much. These chatbots don’t face fatigue the way humans do, or burnout. So they’re able to consistently provide responses with less variation in empathy.
Question: Do chatbots just seem empathetic because they are chattier?
Mr. Chen: We did think of verbosity as a potential confounder in this study. So we set a word count limit for the chatbot responses to keep it in the range of the physician responses. That way, verbosity was no longer a significant factor.
Question: How were quality and empathy measured by the reviewers?
Mr. Chen: For our study we used two teams of readers, each team composed of three physicians. In terms of the actual metrics we used, they were pilot metrics. There are no well-defined measurement scales or checklists that we could use to measure empathy. This is an emerging field of research. So we came up by consensus with our own set of ratings, and we feel that this is an area for the research to define a standardized set of guidelines.
Another novel aspect of this study is that we separated out different dimensions of quality and empathy. A quality response didn’t just mean it was medically accurate — quality also had to do with the focus and completeness of the response.
With empathy there are cognitive and emotional dimensions. Cognitive empathy uses critical thinking to understand the person’s emotions and thoughts and then adjusting a response to fit that. A patient may not want the best medically indicated treatment for their condition, because they want to preserve their quality of life. The chatbot may be able to adjust its recommendation with consideration of some of those humanistic elements that the patient is presenting with.
Emotional empathy is more about being supportive of the patient’s emotions by using expressions like ‘I understand where you’re coming from.’ or, ‘I can see how that makes you feel.’
Question: Why would physicians, not patients, be the best evaluators of empathy?
Mr. Chen: We’re actually very interested in evaluating patient ratings of empathy. We are conducting a follow-up study that evaluates patient ratings of empathy to the same set of chatbot and physician responses,to see if there are differences.
Question: Should cancer patients go ahead and consult chatbots?
Mr. Chen: Although we did observe increases in all of the metrics compared with physicians, this is a very specialized evaluation scenario where we’re using these Reddit questions and responses.
Naturally, we would need to do a trial, a head to head randomized comparison of physicians versus chatbots.
This pilot study does highlight the promising potential of these chatbots to suggest responses. But we can’t fully recommend that they should be used as standalone clinical tools without physicians.
This Q&A was edited for clarity.
Large language models (LLM) such as ChatGPT have shown mixed results in the quality of their responses to consumer questions about cancer.
One recent study found AI chatbots to churn out incomplete, inaccurate, or even nonsensical cancer treatment recommendations, while another found them to generate largely accurate — if technical — responses to the most common cancer questions.
While researchers have seen success with purpose-built chatbots created to address patient concerns about specific cancers, the consensus to date has been that the generalized models like ChatGPT remain works in progress and that physicians should avoid pointing patients to them, for now.
Yet new findings suggest that these chatbots may do better than individual physicians, at least on some measures, when it comes to answering queries about cancer. For research published May 16 in JAMA Oncology (doi: 10.1001/jamaoncol.2024.0836), David Chen, a medical student at the University of Toronto, and his colleagues, isolated a random sample of 200 questions related to cancer care addressed to doctors on the public online forum Reddit. They then compared responses from oncologists with responses generated by three different AI chatbots. The blinded responses were rated for quality, readability, and empathy by six physicians, including oncologists and palliative and supportive care specialists.
Mr. Chen and colleagues’ research was modeled after a 2023 study that measured the quality of physician responses compared with chatbots for general medicine questions addressed to doctors on Reddit. That study found that the chatbots produced more empathetic-sounding answers, something Mr. Chen’s study also found. : quality, empathy, and readability.
Q&A With Author of New Research
Mr. Chen discussed his new study’s implications during an interview with this news organization.
Question: What is novel about this study?
Mr. Chen: We’ve seen many evaluations of chatbots that test for medical accuracy, but this study occurs in the domain of oncology care, where there are unique psychosocial and emotional considerations that are not precisely reflected in a general medicine setting. In effect, this study is putting these chatbots through a harder challenge.
Question: Why would chatbot responses seem more empathetic than those of physicians?
Mr. Chen: With the physician responses that we observed in our sample data set, we saw that there was very high variation of amount of apparent effort [in the physician responses]. Some physicians would put in a lot of time and effort, thinking through their response, and others wouldn’t do so as much. These chatbots don’t face fatigue the way humans do, or burnout. So they’re able to consistently provide responses with less variation in empathy.
Question: Do chatbots just seem empathetic because they are chattier?
Mr. Chen: We did think of verbosity as a potential confounder in this study. So we set a word count limit for the chatbot responses to keep it in the range of the physician responses. That way, verbosity was no longer a significant factor.
Question: How were quality and empathy measured by the reviewers?
Mr. Chen: For our study we used two teams of readers, each team composed of three physicians. In terms of the actual metrics we used, they were pilot metrics. There are no well-defined measurement scales or checklists that we could use to measure empathy. This is an emerging field of research. So we came up by consensus with our own set of ratings, and we feel that this is an area for the research to define a standardized set of guidelines.
Another novel aspect of this study is that we separated out different dimensions of quality and empathy. A quality response didn’t just mean it was medically accurate — quality also had to do with the focus and completeness of the response.
With empathy there are cognitive and emotional dimensions. Cognitive empathy uses critical thinking to understand the person’s emotions and thoughts and then adjusting a response to fit that. A patient may not want the best medically indicated treatment for their condition, because they want to preserve their quality of life. The chatbot may be able to adjust its recommendation with consideration of some of those humanistic elements that the patient is presenting with.
Emotional empathy is more about being supportive of the patient’s emotions by using expressions like ‘I understand where you’re coming from.’ or, ‘I can see how that makes you feel.’
Question: Why would physicians, not patients, be the best evaluators of empathy?
Mr. Chen: We’re actually very interested in evaluating patient ratings of empathy. We are conducting a follow-up study that evaluates patient ratings of empathy to the same set of chatbot and physician responses,to see if there are differences.
Question: Should cancer patients go ahead and consult chatbots?
Mr. Chen: Although we did observe increases in all of the metrics compared with physicians, this is a very specialized evaluation scenario where we’re using these Reddit questions and responses.
Naturally, we would need to do a trial, a head to head randomized comparison of physicians versus chatbots.
This pilot study does highlight the promising potential of these chatbots to suggest responses. But we can’t fully recommend that they should be used as standalone clinical tools without physicians.
This Q&A was edited for clarity.
FROM JAMA ONCOLOGY
Tucatinib-Trastuzumab Benefit ‘Remarkable’ in HER2-positive mCRC
Only about 3% to 5% of patients with metastatic colorectal cancer have tumors that are positive for human epidermal growth factor receptor 2 (HER2), and until recently there was no treatment approved by the US Food and Drug Administration (FDA) for this subset of patients.
That all changed, in January of 2023. At that time, the FDA granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The combination was the first FDA-approved treatment for this patient population.
The only other FDA-approved therapy for metastatic HER2-positive CRC is the antibody-drug conjugate trastuzumab deruxtecan (Enhertu). That drug received accelerated approval from the FDA for metastatic HER2-positive CRC for which no other suitable therapeutic option exists, on April 5, 2024. This FDA action represented an expansion of the drug’s earlier approvals for treating several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer and adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
Drug Combo’s Use With Capecitabine in Breast Cancer
Tucatinib is a potent oral tyrosine kinase inhibitor (TKI) that has been shown to be highly selective for HER2. Prior to approval of the colorectal cancer indication, tucatinib had received FDA approval (in April 2020) in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who had received one or more prior anti-HER2-based regimens in the metastatic setting.
In these patients the combination was associated with significant improvements in both progression-free survival (PFS) and overall survival compared with trastuzumab and capecitabine.
Approval for the colorectal cancer indication was based on results of the phase 2 MOUNTAINEER trial, which were published in The Lancet Oncology.
Real-World Setting
Clinical experience with the combination in a real-world setting is still limited due to the relatively uncommon RAS wild-type HER2-positive CRC subtype, so most of what’s known about the efficacy and safety of tucatinib plus trastuzumab comes from clinical trials. But oncologists interviewed for this article emphasized that the tucatinib-trastuzumab combination nonetheless represents a major breakthrough.
“The population of RAS wild-type HER2-positive is small in colorectal cancer, but the benefit of this treatment is really remarkable. With this combination therapy there was a 38% response rate, and there was a very respectable duration of response. So the population is small, but the benefit of the treatment is by no means small,” said Afsaneh Barzi, MD, PhD, a medical oncologist specializing in gastrointestinal cancers at City of Hope in Duarte, California.
Another medical oncologist interviewed for this piece, who treats patients with HER2-positive metastatic CRC, said that the performance of tucatinib in the real-world setting is in keeping with the efficacy seen in clinical trials.
“There is a group of patients who have a very good response to HER2 [targeted] therapy. Often these are patients who have higher degrees of HER2 amplification, and they do not have concomitant other mutations that activate the pathway, such as RAS mutations,” said Kanwal PS Raghav, MD, MBBS, from the University of Texas MD Anderson Cancer Center in Houston.
Why It Works
In an interview, MOUNTAINEER coinvestigator Tanios S. Bekaii-Saab, MD, from the Mayo Clinic Comprehensive Cancer Center in Phoenix, Arizona, explained why dual HER2 blockade with tucatinib and trastuzumab is an important breakthrough for this population.
“HER2 as a target was already well established in breast cancer and in gastric cancer. In colon cancer we had signals [of anti-HER2 efficacy] but these signals were primarily with dual targeted therapy,” he said.
“What’s unique about tucatinib versus neratinib [Nerlynx], lapatinib [Tykerb] and some of the others is that this is a highly selective tyrosine kinase inhibitor, meaning it is potent just against HER2 and has limited activity against other receptors, classically EGFR, which also goes by the name of HER1,” said MOUNTAINEER trial chair John H. Strickler, MD, of Duke Cancer Center in Durham, North Carolina.
“The reason why that’s valuable is that when you inhibit other receptors like HER1 or EGFR, you can cause significant skin rash and other symptoms that can limit tolerability, which limits your ability to give the full dose. With tucatinib you can more completely inhibit HER2 with fewer side effects,” Dr. Strickler said in an interview.
Dr. Raghav noted that the primary adverse events of therapy with tucatinib have been diarrhea and fatigue, and other common side effects include abdominal pain, fever, nausea, rash, and infusion reactions.
Barriers to Treatment
Dr. Barzi pointed out that in the day-to-day practice setting there are two potential barriers to treatment with tucatinib and trastuzumab for patients with HER2-positive colorectal cancer, hurdles that they would not encounter if they were enrolled in clinical trials.
The first barrier is the requirement for HER2 testing, either through immunohistochemistry or fluorescence in situ hybridization.
“The adoption of HER2 testing in colorectal cancer lags behind other molecular testing, such as testing for KRAS or BRAF, so the provider needs to be aware that HER2 positivity is a possibility,” she said.
The second and more difficult-to-surmount barrier is imposed by the healthcare system. Although the combination is included in National Comprehensive Cancer Network guidelines and, therefore, should not be subject to restrictions or denials by insurers, “the challenge is that this is an oral and IV drug combination,” Dr. Barzi said.
While patients in real-world settings receive intravenous drugs such as trastuzumab in treatment centers, the oral drug component, tucatinib, is dispensed by pharmacies, and patients are often required to shell out high copays for such agents.
Dr. Barzi cited as an example the case of one of her patients who was receiving an oral agent — not tucatinib — for treatment of a different type of colorectal cancer.
“He has very good insurance, and after insurance his out-of-pocket cost on a monthly basis to obtain the drug is $275,” she said.
What’s Next
In colorectal cancer the combination of tucatinib and trastuzumab is approved only in the metastatic setting, but it is also being explored as a first-line therapy in combination with the mFOLFOX6 regimen (5-Fluorouracil, leucovorin, and oxaliplatin) in the MOUNTAINEER-03 trial, which is currently recruiting.
MOUNTAINEER was sponsored by Seagen and Merck. Dr. Strickler reported support from Seagen for the Lancet Oncology manuscript; institutional grants, consulting fees, and travel support from Seagen, and similar relationships with other companies. Dr. Bekaii-Saab reported institutional research and consulting fees from various companies, including Merck, personal consulting fees from various companies, and independent monitoring board/scientific advisory board activities. Dr. Raghav disclosed honoraria and an advisory/consulting role for Seagen and others. Dr. Barzi reported no relevant conflicts of interest.
Only about 3% to 5% of patients with metastatic colorectal cancer have tumors that are positive for human epidermal growth factor receptor 2 (HER2), and until recently there was no treatment approved by the US Food and Drug Administration (FDA) for this subset of patients.
That all changed, in January of 2023. At that time, the FDA granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The combination was the first FDA-approved treatment for this patient population.
The only other FDA-approved therapy for metastatic HER2-positive CRC is the antibody-drug conjugate trastuzumab deruxtecan (Enhertu). That drug received accelerated approval from the FDA for metastatic HER2-positive CRC for which no other suitable therapeutic option exists, on April 5, 2024. This FDA action represented an expansion of the drug’s earlier approvals for treating several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer and adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
Drug Combo’s Use With Capecitabine in Breast Cancer
Tucatinib is a potent oral tyrosine kinase inhibitor (TKI) that has been shown to be highly selective for HER2. Prior to approval of the colorectal cancer indication, tucatinib had received FDA approval (in April 2020) in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who had received one or more prior anti-HER2-based regimens in the metastatic setting.
In these patients the combination was associated with significant improvements in both progression-free survival (PFS) and overall survival compared with trastuzumab and capecitabine.
Approval for the colorectal cancer indication was based on results of the phase 2 MOUNTAINEER trial, which were published in The Lancet Oncology.
Real-World Setting
Clinical experience with the combination in a real-world setting is still limited due to the relatively uncommon RAS wild-type HER2-positive CRC subtype, so most of what’s known about the efficacy and safety of tucatinib plus trastuzumab comes from clinical trials. But oncologists interviewed for this article emphasized that the tucatinib-trastuzumab combination nonetheless represents a major breakthrough.
“The population of RAS wild-type HER2-positive is small in colorectal cancer, but the benefit of this treatment is really remarkable. With this combination therapy there was a 38% response rate, and there was a very respectable duration of response. So the population is small, but the benefit of the treatment is by no means small,” said Afsaneh Barzi, MD, PhD, a medical oncologist specializing in gastrointestinal cancers at City of Hope in Duarte, California.
Another medical oncologist interviewed for this piece, who treats patients with HER2-positive metastatic CRC, said that the performance of tucatinib in the real-world setting is in keeping with the efficacy seen in clinical trials.
“There is a group of patients who have a very good response to HER2 [targeted] therapy. Often these are patients who have higher degrees of HER2 amplification, and they do not have concomitant other mutations that activate the pathway, such as RAS mutations,” said Kanwal PS Raghav, MD, MBBS, from the University of Texas MD Anderson Cancer Center in Houston.
Why It Works
In an interview, MOUNTAINEER coinvestigator Tanios S. Bekaii-Saab, MD, from the Mayo Clinic Comprehensive Cancer Center in Phoenix, Arizona, explained why dual HER2 blockade with tucatinib and trastuzumab is an important breakthrough for this population.
“HER2 as a target was already well established in breast cancer and in gastric cancer. In colon cancer we had signals [of anti-HER2 efficacy] but these signals were primarily with dual targeted therapy,” he said.
“What’s unique about tucatinib versus neratinib [Nerlynx], lapatinib [Tykerb] and some of the others is that this is a highly selective tyrosine kinase inhibitor, meaning it is potent just against HER2 and has limited activity against other receptors, classically EGFR, which also goes by the name of HER1,” said MOUNTAINEER trial chair John H. Strickler, MD, of Duke Cancer Center in Durham, North Carolina.
“The reason why that’s valuable is that when you inhibit other receptors like HER1 or EGFR, you can cause significant skin rash and other symptoms that can limit tolerability, which limits your ability to give the full dose. With tucatinib you can more completely inhibit HER2 with fewer side effects,” Dr. Strickler said in an interview.
Dr. Raghav noted that the primary adverse events of therapy with tucatinib have been diarrhea and fatigue, and other common side effects include abdominal pain, fever, nausea, rash, and infusion reactions.
Barriers to Treatment
Dr. Barzi pointed out that in the day-to-day practice setting there are two potential barriers to treatment with tucatinib and trastuzumab for patients with HER2-positive colorectal cancer, hurdles that they would not encounter if they were enrolled in clinical trials.
The first barrier is the requirement for HER2 testing, either through immunohistochemistry or fluorescence in situ hybridization.
“The adoption of HER2 testing in colorectal cancer lags behind other molecular testing, such as testing for KRAS or BRAF, so the provider needs to be aware that HER2 positivity is a possibility,” she said.
The second and more difficult-to-surmount barrier is imposed by the healthcare system. Although the combination is included in National Comprehensive Cancer Network guidelines and, therefore, should not be subject to restrictions or denials by insurers, “the challenge is that this is an oral and IV drug combination,” Dr. Barzi said.
While patients in real-world settings receive intravenous drugs such as trastuzumab in treatment centers, the oral drug component, tucatinib, is dispensed by pharmacies, and patients are often required to shell out high copays for such agents.
Dr. Barzi cited as an example the case of one of her patients who was receiving an oral agent — not tucatinib — for treatment of a different type of colorectal cancer.
“He has very good insurance, and after insurance his out-of-pocket cost on a monthly basis to obtain the drug is $275,” she said.
What’s Next
In colorectal cancer the combination of tucatinib and trastuzumab is approved only in the metastatic setting, but it is also being explored as a first-line therapy in combination with the mFOLFOX6 regimen (5-Fluorouracil, leucovorin, and oxaliplatin) in the MOUNTAINEER-03 trial, which is currently recruiting.
MOUNTAINEER was sponsored by Seagen and Merck. Dr. Strickler reported support from Seagen for the Lancet Oncology manuscript; institutional grants, consulting fees, and travel support from Seagen, and similar relationships with other companies. Dr. Bekaii-Saab reported institutional research and consulting fees from various companies, including Merck, personal consulting fees from various companies, and independent monitoring board/scientific advisory board activities. Dr. Raghav disclosed honoraria and an advisory/consulting role for Seagen and others. Dr. Barzi reported no relevant conflicts of interest.
Only about 3% to 5% of patients with metastatic colorectal cancer have tumors that are positive for human epidermal growth factor receptor 2 (HER2), and until recently there was no treatment approved by the US Food and Drug Administration (FDA) for this subset of patients.
That all changed, in January of 2023. At that time, the FDA granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The combination was the first FDA-approved treatment for this patient population.
The only other FDA-approved therapy for metastatic HER2-positive CRC is the antibody-drug conjugate trastuzumab deruxtecan (Enhertu). That drug received accelerated approval from the FDA for metastatic HER2-positive CRC for which no other suitable therapeutic option exists, on April 5, 2024. This FDA action represented an expansion of the drug’s earlier approvals for treating several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer and adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
Drug Combo’s Use With Capecitabine in Breast Cancer
Tucatinib is a potent oral tyrosine kinase inhibitor (TKI) that has been shown to be highly selective for HER2. Prior to approval of the colorectal cancer indication, tucatinib had received FDA approval (in April 2020) in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who had received one or more prior anti-HER2-based regimens in the metastatic setting.
In these patients the combination was associated with significant improvements in both progression-free survival (PFS) and overall survival compared with trastuzumab and capecitabine.
Approval for the colorectal cancer indication was based on results of the phase 2 MOUNTAINEER trial, which were published in The Lancet Oncology.
Real-World Setting
Clinical experience with the combination in a real-world setting is still limited due to the relatively uncommon RAS wild-type HER2-positive CRC subtype, so most of what’s known about the efficacy and safety of tucatinib plus trastuzumab comes from clinical trials. But oncologists interviewed for this article emphasized that the tucatinib-trastuzumab combination nonetheless represents a major breakthrough.
“The population of RAS wild-type HER2-positive is small in colorectal cancer, but the benefit of this treatment is really remarkable. With this combination therapy there was a 38% response rate, and there was a very respectable duration of response. So the population is small, but the benefit of the treatment is by no means small,” said Afsaneh Barzi, MD, PhD, a medical oncologist specializing in gastrointestinal cancers at City of Hope in Duarte, California.
Another medical oncologist interviewed for this piece, who treats patients with HER2-positive metastatic CRC, said that the performance of tucatinib in the real-world setting is in keeping with the efficacy seen in clinical trials.
“There is a group of patients who have a very good response to HER2 [targeted] therapy. Often these are patients who have higher degrees of HER2 amplification, and they do not have concomitant other mutations that activate the pathway, such as RAS mutations,” said Kanwal PS Raghav, MD, MBBS, from the University of Texas MD Anderson Cancer Center in Houston.
Why It Works
In an interview, MOUNTAINEER coinvestigator Tanios S. Bekaii-Saab, MD, from the Mayo Clinic Comprehensive Cancer Center in Phoenix, Arizona, explained why dual HER2 blockade with tucatinib and trastuzumab is an important breakthrough for this population.
“HER2 as a target was already well established in breast cancer and in gastric cancer. In colon cancer we had signals [of anti-HER2 efficacy] but these signals were primarily with dual targeted therapy,” he said.
“What’s unique about tucatinib versus neratinib [Nerlynx], lapatinib [Tykerb] and some of the others is that this is a highly selective tyrosine kinase inhibitor, meaning it is potent just against HER2 and has limited activity against other receptors, classically EGFR, which also goes by the name of HER1,” said MOUNTAINEER trial chair John H. Strickler, MD, of Duke Cancer Center in Durham, North Carolina.
“The reason why that’s valuable is that when you inhibit other receptors like HER1 or EGFR, you can cause significant skin rash and other symptoms that can limit tolerability, which limits your ability to give the full dose. With tucatinib you can more completely inhibit HER2 with fewer side effects,” Dr. Strickler said in an interview.
Dr. Raghav noted that the primary adverse events of therapy with tucatinib have been diarrhea and fatigue, and other common side effects include abdominal pain, fever, nausea, rash, and infusion reactions.
Barriers to Treatment
Dr. Barzi pointed out that in the day-to-day practice setting there are two potential barriers to treatment with tucatinib and trastuzumab for patients with HER2-positive colorectal cancer, hurdles that they would not encounter if they were enrolled in clinical trials.
The first barrier is the requirement for HER2 testing, either through immunohistochemistry or fluorescence in situ hybridization.
“The adoption of HER2 testing in colorectal cancer lags behind other molecular testing, such as testing for KRAS or BRAF, so the provider needs to be aware that HER2 positivity is a possibility,” she said.
The second and more difficult-to-surmount barrier is imposed by the healthcare system. Although the combination is included in National Comprehensive Cancer Network guidelines and, therefore, should not be subject to restrictions or denials by insurers, “the challenge is that this is an oral and IV drug combination,” Dr. Barzi said.
While patients in real-world settings receive intravenous drugs such as trastuzumab in treatment centers, the oral drug component, tucatinib, is dispensed by pharmacies, and patients are often required to shell out high copays for such agents.
Dr. Barzi cited as an example the case of one of her patients who was receiving an oral agent — not tucatinib — for treatment of a different type of colorectal cancer.
“He has very good insurance, and after insurance his out-of-pocket cost on a monthly basis to obtain the drug is $275,” she said.
What’s Next
In colorectal cancer the combination of tucatinib and trastuzumab is approved only in the metastatic setting, but it is also being explored as a first-line therapy in combination with the mFOLFOX6 regimen (5-Fluorouracil, leucovorin, and oxaliplatin) in the MOUNTAINEER-03 trial, which is currently recruiting.
MOUNTAINEER was sponsored by Seagen and Merck. Dr. Strickler reported support from Seagen for the Lancet Oncology manuscript; institutional grants, consulting fees, and travel support from Seagen, and similar relationships with other companies. Dr. Bekaii-Saab reported institutional research and consulting fees from various companies, including Merck, personal consulting fees from various companies, and independent monitoring board/scientific advisory board activities. Dr. Raghav disclosed honoraria and an advisory/consulting role for Seagen and others. Dr. Barzi reported no relevant conflicts of interest.
Improved Survival With Everolimus + Endocrine Therapy in HR+/HER2− Advanced BC
Key clinical point: Everolimus plus endocrine therapy (ET) led to promising survival outcomes in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who progressed on a CDK4/6 inhibitor.
Major finding: Everolimus + ET led to a median progression-free survival (mPFS) of 6 months (95% CI 5.3-7.8 months), with longer mPFS observed in patients previously treated with CDK4/6 inhibitors for >18 months (8.7 months; 95% CI 6.6-11.3 months), patients without visceral metastasis (8.0 months; 95% CI 5.8-10.5 months), and chemotherapy-naive patients (7.2 months; 95% CI 5.9-8.4 months).
Study details: This retrospective observational study included 161 patients with HR+/HER2− advanced BC who were previously treated with CDK4/6 inhibitors and received everolimus + ET.
Disclosures: This study did not receive any funding. Several authors declared receiving honoraria, research grants, or travel support from or having other ties with various sources.
Source: Sánchez-Bayona R, Lopez de Sa A, Jerez Gilarranz Y, et al. Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2− advanced breast cancer: A real-world evidence cohort. Breast Cancer Res Treat. 2024 (May 4). doi: 10.1007/s10549-024-07324-8 Source
Key clinical point: Everolimus plus endocrine therapy (ET) led to promising survival outcomes in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who progressed on a CDK4/6 inhibitor.
Major finding: Everolimus + ET led to a median progression-free survival (mPFS) of 6 months (95% CI 5.3-7.8 months), with longer mPFS observed in patients previously treated with CDK4/6 inhibitors for >18 months (8.7 months; 95% CI 6.6-11.3 months), patients without visceral metastasis (8.0 months; 95% CI 5.8-10.5 months), and chemotherapy-naive patients (7.2 months; 95% CI 5.9-8.4 months).
Study details: This retrospective observational study included 161 patients with HR+/HER2− advanced BC who were previously treated with CDK4/6 inhibitors and received everolimus + ET.
Disclosures: This study did not receive any funding. Several authors declared receiving honoraria, research grants, or travel support from or having other ties with various sources.
Source: Sánchez-Bayona R, Lopez de Sa A, Jerez Gilarranz Y, et al. Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2− advanced breast cancer: A real-world evidence cohort. Breast Cancer Res Treat. 2024 (May 4). doi: 10.1007/s10549-024-07324-8 Source
Key clinical point: Everolimus plus endocrine therapy (ET) led to promising survival outcomes in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who progressed on a CDK4/6 inhibitor.
Major finding: Everolimus + ET led to a median progression-free survival (mPFS) of 6 months (95% CI 5.3-7.8 months), with longer mPFS observed in patients previously treated with CDK4/6 inhibitors for >18 months (8.7 months; 95% CI 6.6-11.3 months), patients without visceral metastasis (8.0 months; 95% CI 5.8-10.5 months), and chemotherapy-naive patients (7.2 months; 95% CI 5.9-8.4 months).
Study details: This retrospective observational study included 161 patients with HR+/HER2− advanced BC who were previously treated with CDK4/6 inhibitors and received everolimus + ET.
Disclosures: This study did not receive any funding. Several authors declared receiving honoraria, research grants, or travel support from or having other ties with various sources.
Source: Sánchez-Bayona R, Lopez de Sa A, Jerez Gilarranz Y, et al. Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2− advanced breast cancer: A real-world evidence cohort. Breast Cancer Res Treat. 2024 (May 4). doi: 10.1007/s10549-024-07324-8 Source
Anthracycline and Trastuzumab Tied to Long-Term CVD Risk in BC Survivors
Key clinical point: Chemotherapy with anthracycline or trastuzumab increased the risk for cardiovascular diseases (CVD) in breast cancer (BC) survivors, with the risk persisting beyond 10 years after BC diagnosis and being high in women age < 65 years.
Major finding: Anthracycline or trastuzumab vs no chemotherapy was associated with a 53% higher risk for incident CVD (adjusted hazard ratio [aHR] 1.53; 95% CI 1.31-1.79), particularly in women age < 65 years (aHR 1.70; 95% CI ≥1.19 to ≤2.45). The risk for CVD was seen beyond 5 years after BC diagnosis (aHR5-<10 years 1.85; 95% CI 1.44-2.39; aHR10+ years 1.83; 95% CI 1.34-2.49).
Study details: This retrospective cohort study included 10,211 female BC survivors who received anthracycline or trastuzumab (n = 2712), other chemotherapies (n = 1185), or no chemotherapy (n = 6314), with a median follow-up period of 5.79 years.
Disclosures: This study was supported in part by the Intramural Research Program of the US National Cancer Institute. The authors declared no conflicts of interest.
Source: Vo JB, Ramin C, Veiga LHS, et al. Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in U.S. breast cancer survivors. J Natl Cancer Inst. 2024 (May 8). doi: 10.1093/jnci/djae107 Source
Key clinical point: Chemotherapy with anthracycline or trastuzumab increased the risk for cardiovascular diseases (CVD) in breast cancer (BC) survivors, with the risk persisting beyond 10 years after BC diagnosis and being high in women age < 65 years.
Major finding: Anthracycline or trastuzumab vs no chemotherapy was associated with a 53% higher risk for incident CVD (adjusted hazard ratio [aHR] 1.53; 95% CI 1.31-1.79), particularly in women age < 65 years (aHR 1.70; 95% CI ≥1.19 to ≤2.45). The risk for CVD was seen beyond 5 years after BC diagnosis (aHR5-<10 years 1.85; 95% CI 1.44-2.39; aHR10+ years 1.83; 95% CI 1.34-2.49).
Study details: This retrospective cohort study included 10,211 female BC survivors who received anthracycline or trastuzumab (n = 2712), other chemotherapies (n = 1185), or no chemotherapy (n = 6314), with a median follow-up period of 5.79 years.
Disclosures: This study was supported in part by the Intramural Research Program of the US National Cancer Institute. The authors declared no conflicts of interest.
Source: Vo JB, Ramin C, Veiga LHS, et al. Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in U.S. breast cancer survivors. J Natl Cancer Inst. 2024 (May 8). doi: 10.1093/jnci/djae107 Source
Key clinical point: Chemotherapy with anthracycline or trastuzumab increased the risk for cardiovascular diseases (CVD) in breast cancer (BC) survivors, with the risk persisting beyond 10 years after BC diagnosis and being high in women age < 65 years.
Major finding: Anthracycline or trastuzumab vs no chemotherapy was associated with a 53% higher risk for incident CVD (adjusted hazard ratio [aHR] 1.53; 95% CI 1.31-1.79), particularly in women age < 65 years (aHR 1.70; 95% CI ≥1.19 to ≤2.45). The risk for CVD was seen beyond 5 years after BC diagnosis (aHR5-<10 years 1.85; 95% CI 1.44-2.39; aHR10+ years 1.83; 95% CI 1.34-2.49).
Study details: This retrospective cohort study included 10,211 female BC survivors who received anthracycline or trastuzumab (n = 2712), other chemotherapies (n = 1185), or no chemotherapy (n = 6314), with a median follow-up period of 5.79 years.
Disclosures: This study was supported in part by the Intramural Research Program of the US National Cancer Institute. The authors declared no conflicts of interest.
Source: Vo JB, Ramin C, Veiga LHS, et al. Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in U.S. breast cancer survivors. J Natl Cancer Inst. 2024 (May 8). doi: 10.1093/jnci/djae107 Source
Breast-Conserving Surgery Candidates Can Opt for Neoadjuvant Radiochemotherapy
Key clinical point: Neoadjuvant radiation therapy (NART) led to similar survival outcomes as postoperation radiation therapy (PORT) in patients with invasive ductal carcinoma (IDC) who underwent breast-conserving surgery (BCS) and were treated with neoadjuvant chemotherapy.
Major finding: NART vs PORT led to comparable breast cancer-specific survival (BCCS) and overall survival (OS) outcomes (both log-rank P > .05) in patients undergoing BCS or implant-based immediate breast reconstruction. However, NART vs PORT led to significantly lower BCCS (hazard ratio [HR] 1.407; log-rank P = .003) and OS (HR 1.383; log-rank P = .004) outcomes in those undergoing mastectomy.
Study details: This retrospective study included 14,515 women with IDC (age ≤ 80 years) from the Surveillance, Epidemiology, and End Results (SEER) database who were treated with neoadjuvant chemotherapy, of whom 386 and 14,129 patients underwent NART and PORT, respectively.
Disclosures: This study was supported by Shanghai Science and Technology Commission and Fudan University, China. The authors declared no conflicts of interest.
Source: Yuan J, Zhang M, Wang M, et al. Neoadjuvant radiochemotherapy is safe and feasible for breast conserving surgery or immediate reconstruction. Sci Rep. 2024;14:9208 (Apr 22). doi: 10.1038/s41598-024-59961-0 Source
Key clinical point: Neoadjuvant radiation therapy (NART) led to similar survival outcomes as postoperation radiation therapy (PORT) in patients with invasive ductal carcinoma (IDC) who underwent breast-conserving surgery (BCS) and were treated with neoadjuvant chemotherapy.
Major finding: NART vs PORT led to comparable breast cancer-specific survival (BCCS) and overall survival (OS) outcomes (both log-rank P > .05) in patients undergoing BCS or implant-based immediate breast reconstruction. However, NART vs PORT led to significantly lower BCCS (hazard ratio [HR] 1.407; log-rank P = .003) and OS (HR 1.383; log-rank P = .004) outcomes in those undergoing mastectomy.
Study details: This retrospective study included 14,515 women with IDC (age ≤ 80 years) from the Surveillance, Epidemiology, and End Results (SEER) database who were treated with neoadjuvant chemotherapy, of whom 386 and 14,129 patients underwent NART and PORT, respectively.
Disclosures: This study was supported by Shanghai Science and Technology Commission and Fudan University, China. The authors declared no conflicts of interest.
Source: Yuan J, Zhang M, Wang M, et al. Neoadjuvant radiochemotherapy is safe and feasible for breast conserving surgery or immediate reconstruction. Sci Rep. 2024;14:9208 (Apr 22). doi: 10.1038/s41598-024-59961-0 Source
Key clinical point: Neoadjuvant radiation therapy (NART) led to similar survival outcomes as postoperation radiation therapy (PORT) in patients with invasive ductal carcinoma (IDC) who underwent breast-conserving surgery (BCS) and were treated with neoadjuvant chemotherapy.
Major finding: NART vs PORT led to comparable breast cancer-specific survival (BCCS) and overall survival (OS) outcomes (both log-rank P > .05) in patients undergoing BCS or implant-based immediate breast reconstruction. However, NART vs PORT led to significantly lower BCCS (hazard ratio [HR] 1.407; log-rank P = .003) and OS (HR 1.383; log-rank P = .004) outcomes in those undergoing mastectomy.
Study details: This retrospective study included 14,515 women with IDC (age ≤ 80 years) from the Surveillance, Epidemiology, and End Results (SEER) database who were treated with neoadjuvant chemotherapy, of whom 386 and 14,129 patients underwent NART and PORT, respectively.
Disclosures: This study was supported by Shanghai Science and Technology Commission and Fudan University, China. The authors declared no conflicts of interest.
Source: Yuan J, Zhang M, Wang M, et al. Neoadjuvant radiochemotherapy is safe and feasible for breast conserving surgery or immediate reconstruction. Sci Rep. 2024;14:9208 (Apr 22). doi: 10.1038/s41598-024-59961-0 Source
Statin Use Improves Cancer-Specific Survival in Older Women With Breast Cancer
Key clinical point: Use of a statin after breast cancer (BC) diagnosis improved survival in older women (age ≥ 66 years) with localized and regional stage disease, particularly in those with the hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) subtype.
Major finding: Use vs no use of a statin postdiagnosis was associated with a 15% reduced risk for BC-specific mortality (hazard ratio 0.85; 95% CI 0.75-0.96), with the effect being more pronounced women with HR+/HER2− BC (hazard ratio 0.71; 95% CI 0.57-0.88). There was no significant association between postdiagnosis statin use and the risk for BC recurrence (hazard ratio 1.05; 95% CI 0.91-1.21).
Study details: This retrospective cohort study included women with localized and regional stage BC from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were assessed for mortality (n = 38,858) and recurrence (n = 28,522), of whom 8836 and 6475 used a statin postdiagnosis, respectively.
Disclosures: This study was supported by the US National Cancer Institute, National Institutes of Health. The authors declared no conflicts of interest.
Source: Guo H, Malone KE, Heckbert SR, Li CI. Statin use and risks of breast cancer recurrence and mortality. Cancer. 2024 (May 6). doi: 10.1002/cncr.35362 Source
Key clinical point: Use of a statin after breast cancer (BC) diagnosis improved survival in older women (age ≥ 66 years) with localized and regional stage disease, particularly in those with the hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) subtype.
Major finding: Use vs no use of a statin postdiagnosis was associated with a 15% reduced risk for BC-specific mortality (hazard ratio 0.85; 95% CI 0.75-0.96), with the effect being more pronounced women with HR+/HER2− BC (hazard ratio 0.71; 95% CI 0.57-0.88). There was no significant association between postdiagnosis statin use and the risk for BC recurrence (hazard ratio 1.05; 95% CI 0.91-1.21).
Study details: This retrospective cohort study included women with localized and regional stage BC from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were assessed for mortality (n = 38,858) and recurrence (n = 28,522), of whom 8836 and 6475 used a statin postdiagnosis, respectively.
Disclosures: This study was supported by the US National Cancer Institute, National Institutes of Health. The authors declared no conflicts of interest.
Source: Guo H, Malone KE, Heckbert SR, Li CI. Statin use and risks of breast cancer recurrence and mortality. Cancer. 2024 (May 6). doi: 10.1002/cncr.35362 Source
Key clinical point: Use of a statin after breast cancer (BC) diagnosis improved survival in older women (age ≥ 66 years) with localized and regional stage disease, particularly in those with the hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) subtype.
Major finding: Use vs no use of a statin postdiagnosis was associated with a 15% reduced risk for BC-specific mortality (hazard ratio 0.85; 95% CI 0.75-0.96), with the effect being more pronounced women with HR+/HER2− BC (hazard ratio 0.71; 95% CI 0.57-0.88). There was no significant association between postdiagnosis statin use and the risk for BC recurrence (hazard ratio 1.05; 95% CI 0.91-1.21).
Study details: This retrospective cohort study included women with localized and regional stage BC from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were assessed for mortality (n = 38,858) and recurrence (n = 28,522), of whom 8836 and 6475 used a statin postdiagnosis, respectively.
Disclosures: This study was supported by the US National Cancer Institute, National Institutes of Health. The authors declared no conflicts of interest.
Source: Guo H, Malone KE, Heckbert SR, Li CI. Statin use and risks of breast cancer recurrence and mortality. Cancer. 2024 (May 6). doi: 10.1002/cncr.35362 Source