FDA Approves Elacestrant for ER+/HER2- Advanced Breast Cancer


Elacestrant has recieved FDA approval for the treatment of patients with estrogen receptor-positive/HER2-negative advanced or metastatic breast cancer.

The FDA has approved elacestrant (Orserdu), an oral selective estrogen receptor degrader (SERD), for use in patients with estrogen receptor (ER)-positive/HER2-negative advanced or metastatic breast cancer.1

Elacestrant is the first oral SERD that has shown improved efficacy over standard of care (SOC) treatments in patients with advanced breast cancer.2 The approval was based on data from the phase 3 EMERALD trial (NCT03778931), which randomly assigned patients to receive elacestrant or investigator’s choice of SOC following 1 or 2 prior lines of endocrine therapy including CDK4/6 therapy.

In the EMERALD trial, elacestrant met its co-primary end points 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 vs 1.9 months with SOC.2 In patients with a confirmed ESR1 mutation (47.8%), elacestrant reduced the risk of progression by 45% (HR, 0.55; 95% CI, 0.39-0.77; P = .0005).

The trial population consisted of 477 patients who were randomly assigned 1:1 to receive elacestrant or SOC. They were well-balanced based on baseline characteristics, and were stratified by ESR1 status, visceral metastases, and previous treatment with fulvestrant (Faslodex). Patients in the experimental arm received 400 mg of elacestrant orally once daily. SOC treatment was investigator’s choice of fulvestrant, anastrozole (Arimidex), letrozole (Femara), or exemestane (Aromasin) monotherapy, according to label and prescribed based on which prior treatments had been used.

Landmark analyses of PFS were conducted at 6 months and 12 months. The 6-month PFS rate was 34.3% (95% CI, 27.2%-41.5%) for elacestrant vs 20.4% (95% CI, 14.1%-26.7%) for SOC, whereas the 12-month PFS rate was 22.3% (95% CI, 15.2%-29.4%) vs 9.4% (95% CI, 4.0%-14.8%), respectively.

In a prespecified interim overall survival (OS) analysis, there were 149 OS events, with a hazard ratio of 0.75 favoring elacestrant (95% CI, 0.54-1.04; P = .08).

In terms of safety, adverse events (AEs) occurred in 92.0% of patients who received elacestrant vs 86.0% in the SOC arm, but 63.3% and 43.7%, respectively, were deemed treatment-related by investigators. Grade 3 or 4 AEs occurred in 27.0% in the elacestrant arm and 20.5% in the SOC arm, whereas only 7.2% and 3.1% were deemed treatment-related AEs. AEs led to discontinuation in 15 patients (6.3%) in the elacestrant arm and 10 patients (4.4%) in the SOC arm. The most common any-grade AE was nausea in 35.0% of the elacestrant arm and 18.8% of the SOC arm; grade 3 nausea occurred in 2.5% of the elacestrant arm and 0.9% of the SOC arm.

1. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. News Release. FDA. January 27, 2023. Accessed January 27, 2023. https://bit.ly/3WHsEq8
2. Bidard FC, Kaklamani VG, Neven P, et al. 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. J Clin Oncol. 2022;40(28):3246-3256. doi:10.1200/JCO.22.00338
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