ESR1 Mutations in HR+ Breast Cancer - Episode 4
Kevin Kalinsky, MD, MS, gives an overview of recent data from the EMERALD trial investigating elacestrant in patients with ER+/HER2- advanced breast cancer.
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 discussed emerging data on elacestrant, the first oral selective estrogen receptor degrader (SERD) approved in breast cancer. The phase III EMERALD trial compared elacestrant to physician’s choice of endocrine therapy in patients previously treated with CDK4/6 inhibitors, about 20% also having prior fulvestrant exposure.
Elacestrant improved progression-free survival over endocrine therapy specifically in the 30% to 40% of patients with baseline ESR1 mutations. Additional EMERALD analyses suggest duration of prior CDK4/6 inhibitor therapy may predict elacestrant benefit. No significant difference was seen between arms for patients on CDK4/6 inhibitor <6 months. However, those remaining on CDK4/6 inhibitor ≥12 months derived substantial incremental progression-free survival from elacestrant over endocrine options.
Dr Kevin Kalinsky shared that in practice, he utilizes elacestrant monotherapy per its indication. The ≥12-month CDK4/6 duration analysis suggests retained endocrine sensitivity, supporting preferential efficacy of subsequent SERD therapy. Additional EMERALD analyses reinforced this CDK4/6 duration effect persisted across patient subgroups including co-occurring PIK3CA mutations or HER2-low status.
Drs. Mayer and Kalinsky believe these data collectively suggest CDK4/6 inhibitor duration may emerge as a clinical marker informing optimal SERD sequencing. Elacestrant appears particularly effective in patients retaining sufficient endocrine sensitivity as evidenced by sustained prior CDK4/6 response over 12 months. More intensive therapy may be reserved for those exhibiting earlier primary resistance. Defining molecular determinants of response and resistance will further optimize HR+ breast cancer therapy sequencing.
*Video synopsis is AI-generated and reviewed by OncLive editorial staff.