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, MD^1,2; 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, MD^24,25,26,27; 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

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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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