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

Author(s): Francois-Clement Bidard, MD1,2; Virginia G. Kaklamani, MD3; Patrick Neven, MD4; Guillermo Streich, MD5; Alberto J. Montero, MD6; Frédéric Forget, MD7; Marie-Ange Mouret-Reynier, MD8; Joo Hyuk Sohn, MD9; Donatienne Taylor, MD10; Kathleen K. Harnden, MD11; Hung Khong, MD12; Judit Kocsis, MD13; Florence Dalenc, MD14; Patrick M. Dillon, MD15; Sunil Babu, MD16; Simon Waters, MD17; Ines Deleu, MD18; José A. García Sáenz, MD19; Emilio Bria, MD20; Marina Cazzaniga, MD21; Janice Lu, MD22; Philippe Aftimos, MD23; Javier Cortés, MD24,25,26,27; Shubin Liu, MS28; Giulia Tonini, PhD29; Dirk Laurent, MD30; Nassir Habboubi, MD31; Maureen G. Conlan, MD32; and Aditya Bardia, MD33
Source: 10.1200/JCO.22.00338 Journal of Clinical Oncology 40, no. 28 (October 01, 2022) 3246-3256
Maem Hussein MD

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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 cyclindependent 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 5 239) or SOC (n 5 238). 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 5 0.70; 95% CI, 0.55 to 0.88; P 5 .002) and patients with ESR1 mutation (hazard ratio 5 0.55; 95% CI, 0.39 to 0.77; P 5 .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.

Author Affiliations

1Institut Curie, Paris and Saint Cloud, France; 2Versailles Saint Quentin/Paris-Saclay University, Saint Cloud, France; 3University of Texas Health Sciences Center, San Antonio, TX; 4Universitaire Ziekenhuizen (UZ)—Leuven Cancer Institute, Leuven, Belgium; 5Centro Médico Austral, Buenos Aires, Argentina; 6University Hospitals Seidman Cancer Center-Case Western Reserve University, Cleveland, OH; 7Centre Hospitalier de l’Ardenne—Site de Libramont, Libramont-Chevigny, Belgium; 8Centre Jean Perrin, Clermont-Ferrand, France; 9Yonsei Cancer Center, Yonsei University Health System-Medical Oncology, Seoul, Republic of Korea; 10Université catholique de Louvain, CHU UCL Namur—Site Sainte-Elisabeth, Namur, Belgium; 11Inova Schar Cancer Institute, Fairfax, Virginia; 12Moffit Cancer Center & Research Institute, Tampa, FL; 13Bács-Kiskun Megyei Kórház, Kecskemét, Hungary; 14Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France; 15University of Virginia Cancer Center, Charlottesville, VA; 16Fort Wayne Medical Oncology and Hematology, Fort Wayne, IN; 17Velindre Cancer Centre, Cardiff, United Kingdom; 18AZ Nikolaas, Sint-Niklaas, Belgium; 19Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), Madrid, Spain; 20Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 21Ospedale San Gerardo-ASST Monza, Monza, Italy; 22University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA; 23Institut Jules Bordet – Université Libre de Bruxelles, Brussels, Belgium; 24International Breast Cancer Center (IBCC), Quironsalud Group, Barcelona, Spain; 25Scientific Department, Medica Scientia Innovation Research, Valencia, Spain; 26Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 27Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain; 28Cytel, Waltham, MA; 29Menarini Group, Florence, Italy; 30Berlin Chemie AG/Menarini Group, Berlin, Germany; 31Stemline Therapeutics/Menarini Group, New York, NY; 32Radius Health, Inc, Boston, MA; 33Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA

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