Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial
Purpose: Patients with pretreated estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer have a poor prognosis. Elacestrant is a novel oral selective ER degrader that showed promising activity in early studies.
Methods: This randomized, open-label, phase III trial enrolled patients with ER-positive/HER2-negative advanced breast cancer who had received one to two lines of endocrine therapy, required pretreatment with a cyclin-dependent kinase 4/6 inhibitor, and had been treated with up to one chemotherapy regimen. Patients were randomly assigned to receive either elacestrant 400 mg orally once daily or standard-of-care (SOC) endocrine monotherapy. The primary endpoints were progression-free survival (PFS) as assessed by blinded independent central review in all patients and in those with detectable ESR1 mutations.
Results: Patients were randomly assigned to elacestrant (n = 239) or SOC (n = 238). ESR1 mutations were detected in 47.8% of patients, and 43.4% had received two prior endocrine therapies. PFS was significantly prolonged in all patients (hazard ratio [HR] = 0.70; 95% CI, 0.55 to 0.88; P = .002) and in patients with ESR1 mutations (HR = 0.55; 95% CI, 0.39 to 0.77; P = .0005). Treatment-related grade 3/4 adverse events occurred in 7.2% of patients receiving elacestrant and 3.1% of those receiving SOC. Treatment-related adverse events leading to discontinuation were 3.4% in the elacestrant arm versus 0.9% in the SOC arm. Nausea of any grade was reported in 35.0% of patients receiving elacestrant and 18.8% of those receiving SOC (grade 3/4, 2.5% and 0.9%, respectively).
Conclusion: Elacestrant is the first oral selective ER degrader to demonstrate a significant improvement in PFS compared to SOC in both the overall population and in patients with ESR1 mutations. It also showed a manageable safety profile in a phase III trial for patients with ER-positive/HER2-negative advanced breast cancer.