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
Open accessAbstract
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.
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Use of fulvestrant as a single agent is now suboptimal in the second line.
“the use of which as a single-agent is now suboptimal in the second line”
From Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3. (2024) · cites this paper as [23]
The Discussion (page not provided) says fulvestrant combinations are increasingly used as second-line standard care in certain regions, particularly for PIK3CA-mutant disease, and reports better outcomes with elacestrant than with fulvestrant alone. It also says single-agent endocrine therapy remains appropriate for some patients, so it does not establish that fulvestrant monotherapy is generally suboptimal in the second line. (LLM, conf=0.83)
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- Authors
- Bidard, F.-C., Kaklamani, V. G., Neven, P., Streich, G., Montero, A. J., Forget, F., Mouret-Reynier, M.-A., Sohn, J. H., Taylor, D., Harnden, K. K., Khong, H., Kocsis, J., Dalenc, F., Dillon, P. M., Babu, S., Waters, S., Deleu, I., García Sáenz, J. A., Bria, E., Cazzaniga, M., Lu, J., Aftimos, P., Cortés, J., Liu, S., Tonini, G., Laurent, D., Habboubi, N., Conlan, M. G., & Bardia, A.
- Affiliations
- Institut Curie, Paris and Saint Cloud, France
- The University of Texas at San Antonio Health Science Center (US)
- Universitair Ziekenhuis Leuven (BE)
- Centro Médico Austral, Buenos Aires, Argentina
- University Hospitals Seidman Cancer Center (US)
- Centre Hospitalier de l'Ardenne—Site de Libramont, Libramont-Chevigny, Belgium
- Centre Jean Perrin, Clermont-Ferrand, France
- Yonsei Cancer Center, Yonsei University Health System-Medical Oncology, Seoul, Republic of Korea
- UCLouvain (BE)
- Inova Fairfax Hospital (US)
- Moffitt Cancer Center (US)
- Bács-Kiskun Megyei Kórház (HU)
- Institut Claudius Regaud (FR)
- University of Virginia Cancer Center (US)
- Fort Wayne Medical Oncology and Hematology, Fort Wayne, IN
- Velindre Cancer Centre (GB)
- AZ Nikolaas, Sint-Niklaas, Belgium
- Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), Madrid, Spain
- Università Cattolica del Sacro Cuore (IT)
- Azienda Ospedaliera San Gerardo (IT)
- USC Norris Comprehensive Cancer Center (US)
- Institut Jules Bordet (BE)
- MedSIR (Spain) (ES)
- Cytel (United States) (US)
- Menarini Group (Italy) (IT)
- Menarini Group (Germany) (DE)
- Stemline Therapeutics (United States) (US)
- Radius Health (United States) (US)
- Harvard University (US)
- Corresponding author
- Bardia, Aditya
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2022-10-01
- Volume
- 40
- Issue
- 28
- Pages
- 3246-3256
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC9553388
- OpenAlex
- W4280490473
- Cited by
- 777
- References
- 4
- Citations by year
- 2026: 190 · 2025: 205 · 2024: 205 · 2023: 154 · 2022: 22 · 2020: 1
- FWCI
- 94.70
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-06-26)
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of Clinical Oncology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lirias (submittedVersion, cc-by-nc-nd)
- HAL (submittedVersion, cc-by-nc-nd)
- BOA (University of Milano-Bicocca) (submittedVersion, cc-by-nc-nd)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
- Funders
- Radius Health
- Menarini Group
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- elacestrant, selective estrogen receptor degrader, estrogen receptor-positive breast cancer, HER2-negative breast cancer, advanced breast cancer, endocrine therapy, ESR1 mutations, progression-free survival, CDK4/6 inhibitors, nausea, treatment safety
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Estrogen Antagonists, Female, Humans, Receptors, Estrogen, Tetrahydronaphthalenes, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Cyclin-Dependent Kinase 4
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