Elacestrant Improves PFS vs Endocrine Monotherapy in ER-Positive/HER2-Negative Advanced Breast Cancer

Elacestrant, a novel, oral selective estrogen receptor degrader (SERD), yielded improved progression-free survival (PFS) vs standard of care endocrine monotherapy among patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, according to results from the phase 3 EMERALD trial. This is the first oral, SERD to demonstrate in a phase 3 trial a significant progression-free survival improvement compared to standard of care, both in the overall population and in patients with ESR1 mutations, with manageable safety for patients with ER-positive/HER2-negative advanced breast cancer.

The EMERALD trial enrolled 477 patients with ER-positive/HER2-negative breast adenocarcinoma between February 2019 and October 2020. Patients were randomized in a 1:1 ratio to receive 400 mg oral elacestrant once daily (n = 239) or standard of care endocrine monotherapy, per investigator’s choice of fulvestrant, anastrozole, letrozole, or exemestrane, intravenously once every 3 weeks (n = 238). The primary end points of the trial were blinded independent central review (BICR)-assessed progression-free survival in all patients as well as in patients with detectable ESR1 mutations (n = 228). Secondary end points included safety and tolerability.

At the data cutoff of September 6, 2021, the median follow-up was 15.1 months. All patients, and patients with ESR1 mutation treated with elacestrant showed a statistically significant improvement of PFS (hazard ratio = 0.70; 95% confidence interval, 0.55 to 0.88; P = .002 and hazard ratio = 0.55; 95% confidence interval, 0.39 to 0.77, P =.0005, respectively). According to landmark analyses, PFS rates at both 6 and 12 months were improved in the elacestrant arm compared to the standard of care arm, for all patients and patients with ESR1 mutation.

Serious treatment-related adverse events were reported in 7.2% of patients in the elacestrant group and 3.1% in the standard of care group, leading to discontinuation of treatment in 3.4% of patients receiving elestrant vs 0.9% receiving standard of care. The most common treatment-related adverse event was nausea, occurring in 35% and 18% of patients in the elacestrant and standard of care arms, respectively. Elecestrant yielded grade 3/4 nausea in 2.5% of patients vs 0.9% with standard of care. There were no treatment-related deaths reported in either arm.

“These data represent an opportunity to potentially offer a new oral endocrine therapy option to patients with previously treated metastatic hormone receptor–positive breast cancer, including ESR1-mutant breast cancer,” concluded the study authors.

Source:                                        

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. May 18, 2022. doi:10.1200/JCO.22.00338