ESR1 Mutations in HR+ Breast Cancer - Episode 5
The Role of Elacestrant in Breast Cancer
Erica L. Mayer, MD, MPH, discusses the role of elacestrant in the breast cancer treatment landscape and provides clinical insights on its safety profile.
This is a synopsis of an Insights series featuring Kevin Kalinsky, MD, MS, of Winship Cancer Institute of Emory University, and Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute.
Dr Erica Mayer shares she utilizes the oral selective estrogen receptor degrader [SERD] elacestrant in practice per data suggesting longer duration of prior CDK4/6 inhibitor therapy predicts enhanced efficacy. This aligns with interpreting extended CDK4/6 duration as a marker of retained endocrine sensitivity rather than imminent resistance, supporting subsequent intensified estrogen pathway blockade.
In the phase III EMERALD trial, elacestrant improved progression-free survival over physician’s choice endocrine therapy specifically in patients on prior CDK4/6 inhibitors for ≥12 months. Dr Mayer often applies elacestrant in long-term CDK4/6 responders progressing after years of therapy, where further endocrine options are preferred based on the clinical context.
Additional EMERALD analyses highlighted elacestrant’s favorable toxicity profile with primarily low-grade nausea and no concerning safety signals, enabling flexible sequencing with other therapies. For instance, in patients harboring co-occurring ESR1 and PIK3CA mutations, both actionable alterations, Dr Mayer utilizes elacestrant first considering its more favorable toxicity over PI3K inhibitors before subsequently deploying PIK3CA-targeted therapy.
Dr Kevin Kalinsky noted that with expanding targeted therapy options in metastatic HR+ disease, including PI3K and AKT inhibition, treatment selection requires balancing efficacy and quality of life. He similarly prioritizes elacestrant in lower burden clinical scenarios where leveraging endocrine activity remains suitable, while utilizing more intensive regimens like fulvestrant/alpelisib for patients requiring rapid disease control.
Overall, Drs Mayer and Kalinsky believe elacestrant’s emergence helps fill a major unmet need in HR+ metastatic breast cancer. Its oral administration and tolerability provide a long-awaited endocrine sequencing option. Subpopulation analyses continue to refine appropriate patient selection, with duration of prior CDK4/6 response strongly indicating retained sensitivity to endocrine mechanisms.
*Video synopsis is AI-generated and reviewed by OncLive editorial staff.
Related Content:
