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
Francois-Clement Bidard, Virginia G Kaklamani, Patrick Neven, Guillermo Streich, Alberto J Montero, Frédéric Forget, Marie-Ange Mouret-Reynier, Joo Hyuk Sohn, Donatienne Taylor, Kathleen K Harnden, Hung Khong, Judit Kocsis, Florence Dalenc, Patrick M Dillon, Sunil Babu, Simon Waters, Ines Deleu, José A García Sáenz, Emilio Bria, Marina Cazzaniga, Janice Lu, Philippe Aftimos, Javier Cortés, Shubin Liu, Giulia Tonini, Dirk Laurent, Nassir Habboubi, Maureen G Conlan, Aditya Bardia, Francois-Clement Bidard, Virginia G Kaklamani, Patrick Neven, Guillermo Streich, Alberto J Montero, Frédéric Forget, Marie-Ange Mouret-Reynier, Joo Hyuk Sohn, Donatienne Taylor, Kathleen K Harnden, Hung Khong, Judit Kocsis, Florence Dalenc, Patrick M Dillon, Sunil Babu, Simon Waters, Ines Deleu, José A García Sáenz, Emilio Bria, Marina Cazzaniga, Janice Lu, Philippe Aftimos, Javier Cortés, Shubin Liu, Giulia Tonini, Dirk Laurent, Nassir Habboubi, Maureen G Conlan, Aditya Bardia
Abstract
Purpose: Patients with pretreated estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer have poor prognosis. Elacestrant is a novel, oral selective ER degrader that demonstrated activity in early studies.
Methods: This randomized, open-label, phase III trial enrolled patients with ER-positive/HER2-negative advanced breast cancer who had one-two lines of endocrine therapy, required pretreatment with a cyclin-dependent kinase 4/6 inhibitor, and ≤ 1 chemotherapy. Patients were randomly assigned to elacestrant 400 mg orally once daily or standard-of-care (SOC) endocrine monotherapy. Primary end points were progression-free survival (PFS) by blinded independent central review in all patients and patients with detectable ESR1 mutations.
Results: Patients were randomly assigned to elacestrant (n = 239) or SOC (n = 238). ESR1 mutation was detected in 47.8% of patients, and 43.4% received two prior endocrine therapies. PFS was prolonged in all patients (hazard ratio = 0.70; 95% CI, 0.55 to 0.88; P = .002) and patients with ESR1 mutation (hazard ratio = 0.55; 95% CI, 0.39 to 0.77; P = .0005). Treatment-related grade 3/4 adverse events occurred in 7.2% receiving elacestrant and 3.1% receiving SOC. Treatment-related adverse events leading to treatment discontinuations were 3.4% in the elacestrant arm versus 0.9% in SOC. Nausea of any grade occurred in 35.0% receiving elacestrant and 18.8% receiving SOC (grade 3/4, 2.5% and 0.9%, respectively).
Conclusion: Elacestrant is the first oral selective ER degrader demonstrating a significant PFS improvement versus SOC both in the overall population and in patients with ESR1 mutations with manageable safety in a phase III trial for patients with ER-positive/HER2-negative advanced breast cancer.
Trial registration: ClinicalTrials.gov NCT03778931.
Conflict of interest statement
Aditya Bardia
Consulting or Advisory Role: Novartis, Genentech, Pfizer, Spectrum Pharmaceuticals, bioTheranostics, Merck, Radius Health, Immunomedics (Inst), Novartis (Inst), Genentech/Roche (Inst), Pfizer (Inst), Radius Health (Inst), Innocrin Pharma (Inst), Immunomedics, Sanofi, Puma Biotechnology, Daiichi Sankyo/Astra Zeneca, Foundation Medicine, Philips Healthcare
Research Funding: Genentech (Inst), Novartis (Inst), Pfizer (Inst), Merck (Inst), Sanofi (Inst), Radius Health (Inst), Immunomedics (Inst), AstraZeneca/Daiichi Sankyo (Inst)
Open Payments Link: https://openpaymentsdata.cms.gov/physician/523675
No other potential conflicts of interest were reported.
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