The FDA has approved elacestrant (Orserdu), an oral selective estrogen receptor degrader (SERD), for patients with estrogen receptor (ER)-positive/HER2-negative advanced or metastatic breast cancer. This approval represents a significant milestone as elacestrant is the first oral SERD that has shown improved efficacy over standard of care treatments in patients with advanced breast cancer.
EMERALD Trial Results Drive Approval
The approval was based on data from the phase 3 EMERALD trial (NCT03778931), which randomly assigned 477 patients to receive elacestrant or investigator's choice of standard of care following 1 or 2 prior lines of endocrine therapy including CDK4/6 therapy. Patients were well-balanced based on baseline characteristics and stratified by ESR1 status, visceral metastases, and previous treatment with fulvestrant.
Elacestrant met its co-primary endpoints of progression-free survival (PFS) in all patients. At 15.5 months median follow-up, elacestrant reduced the risk of progression or death by 30% (HR, 0.70; 95% CI, 0.55-0.88; P = .0018) in all patients, with a median PFS of 2.8 months for elacestrant versus 1.9 months with standard of care.
Enhanced Efficacy in ESR1-Mutated Patients
The treatment demonstrated particularly strong efficacy in patients with confirmed ESR1 mutations, who comprised 47.8% of the trial population. In this subgroup, elacestrant reduced the risk of progression by 45% (HR, 0.55; 95% CI, 0.39-0.77; P = .0005) compared to standard of care.
Landmark analyses revealed sustained benefit over time. The 6-month PFS rate was 34.3% (95% CI, 27.2%-41.5%) for elacestrant versus 20.4% (95% CI, 14.1%-26.7%) for standard of care, while the 12-month PFS rate was 22.3% (95% CI, 15.2%-29.4%) versus 9.4% (95% CI, 4.0%-14.8%), respectively.
Treatment Protocol and Safety Profile
Patients in the experimental arm received 400 mg of elacestrant orally once daily. Standard of care treatment was investigator's choice of fulvestrant, anastrozole, letrozole, or exemestane monotherapy, prescribed based on which prior treatments had been used.
In terms of safety, adverse events occurred in 92.0% of patients who received elacestrant versus 86.0% in the standard of care arm, but 63.3% and 43.7%, respectively, were deemed treatment-related by investigators. Grade 3 or 4 adverse events occurred in 27.0% in the elacestrant arm and 20.5% in the standard of care arm, whereas only 7.2% and 3.1% were deemed treatment-related adverse events.
The most common any-grade adverse event was nausea in 35.0% of the elacestrant arm and 18.8% of the standard of care arm; grade 3 nausea occurred in 2.5% of the elacestrant arm and 0.9% of the standard of care arm. Adverse events led to discontinuation in 15 patients (6.3%) in the elacestrant arm and 10 patients (4.4%) in the standard of care arm.
Overall Survival Trends
In a prespecified interim overall survival analysis, there were 149 overall survival events, with a hazard ratio of 0.75 favoring elacestrant (95% CI, 0.54-1.04; P = .08), suggesting a potential survival benefit that will require longer follow-up to confirm statistical significance.
