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

Dr. Maen Hussein's Thoughts

Coming soon to a pharmacy near you?

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

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Phase III Randomized, Placebo-Controlled Clinical Trial of Donepezil for Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy (WF-97116)

It seems donepezil did not show any cognitive benefit when added to standard adjuvant chemotherapy for breast cancer. Unfortunately, adequate treatment for ‘chemo-brain’ remains elusive. There is data that a lipid structure, S1P, may be linked to this process and may be ‘druggable’ with some of the MS agents.

Read More »

Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study

Datopotamab Deruxtecan is a new ADC that will likely be approved in the near future. The payload is the same as used in Enhertu, but the antibody is directed at TROP2. This report is from the TROPION-pan tumor study and shows a promising ORR in HR+/HER2- MBC. There is reasonable data for this compound in 2L met-NSCLC in the TROPION-LUNG01 study with an improvement in PFS compared to docetaxel of 4.4 vs 3.7 months. Dato also is effective in patients with actionable genetic alterations in the 2L setting. There is also an ongoing study on its use in the 1L setting for met-NSCLC in combination with pembrolizumab and chemotherapy.

Read More »

Final results of RIGHT Choice: Ribociclib plus endocrine therapy vs combination chemotherapy in premenopausal women with clinically aggressive HR+/HER2− advanced breast cancer

Nicely done study comparing Ribociclib + ET vs chemotherapy in premenopausal high-risk HR+, HER2-neg patients felt to be high risk. Results showed better efficacy (PFS), tolerability and similar response rates. Of note, >80% of patients had visceral disease or were felt to be rapid progressors. Anti-hormone-based therapy remains king in the HR+ setting.

Read More »