Phase 3 EMERALD Study of Elacestrant
Panelists discuss the evolving management of estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer, highlighting the clinical impact of oral selective estrogen receptor degraders (SERDs)—particularly in patients with ESR1 mutations—while emphasizing the importance of biomarker-guided therapy selection and ongoing reassessment to optimize outcomes in the context of prior endocrine and CDK4/6 inhibitor exposure.
This session focused on the evolving treatment landscape for ER-positive, HER2-negative metastatic breast cancer, with particular attention to the use of oral endocrine therapies targeting ESR1 mutations. A key topic was the first FDA-approved oral SERD, which has shown promising results in this setting. The data reviewed stemmed from a large phase 3 trial that compared the agent with standard endocrine monotherapy options, including aromatase inhibitors and fulvestrant, in patients who had already received 1 to 2 prior lines of endocrine therapy and prior CDK4/6 inhibitors.
The trial results highlighted improved median progression-free survival for those receiving the oral SERD, particularly in a subset of patients whose disease demonstrated endocrine sensitivity. This was primarily defined by a duration of at least one year on first-line CDK4/6 inhibitor therapy. Patients with ESR1 mutations appeared to benefit most significantly, with median progression-free survival reaching around 8 to 9 months. These findings are especially notable given that the study population included patients who had already received significant prior treatment, including chemotherapy in a portion of cases.
A key takeaway was the critical role of biomarker selection—specifically the presence of ESR1 mutations—in determining which patients may benefit most from these novel therapies. These mutations are relatively rare at initial metastatic diagnosis but become more prevalent following endocrine therapy, reinforcing the need for reassessment as treatment progresses. The discussion underscored the importance of understanding molecular drivers of resistance and using them to guide therapy decisions in advanced disease. As newer agents and trials continue to emerge, the ability to match patients to the most appropriate therapies based on their tumor biology will become increasingly central to optimizing outcomes in metastatic breast cancer.
