HR+ Breast Cancer: Treatment Advances and Highlights from ASCO 2025 - Episode 3
Panelists discuss how elacestrant from the EMERALD trial is being incorporated into practice based on ESR1 mutation status and duration of prior CDK4/6 inhibitor therapy, with combination approaches being explored in the ELEVATE trial.
Elacestrant Implementation and Biomarker-Driven Treatment Decisions
The Emerald trial established elacestrant as an important oral selective estrogen receptor degrader (SERD) option for patients with estrogen receptor–positive metastatic breast cancer who have progressed on CDK4/6 inhibitor therapy. This phase 3 study enrolled over 400 patients who had received prior endocrine therapy and CDK4/6 inhibitors, with approximately 20% to 25% having received chemotherapy. The trial results demonstrated a modest progression-free survival advantage in the overall population, with the benefit primarily driven by patients harboring ESR1 mutations.
Subgroup analysis reveals that duration of prior CDK4/6 inhibitor therapy serves as a valuable biomarker for predicting elacestrant efficacy. Patients who received CDK4/6 inhibitor therapy for 12 months or longer achieved approximately 8.6 months of progression-free survival compared with 4 months for those with shorter durations of 6 months or less. This biomarker helps clinicians identify patients with endocrine-sensitive disease who are most likely to benefit from continued endocrine-based therapy.
Clinical implementation focuses on patients with ESR1 mutations who demonstrated prolonged benefit from prior CDK4/6 inhibitor therapy, regardless of comutations or ESR1 variant types. The data support using elacestrant in combination with other targeted therapies, with ongoing trials exploring various combination strategies. This approach allows clinicians to maximize the benefit of oral SERD therapy while maintaining quality of life through oral administration rather than intramuscular fulvestrant injections.