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Updated: May 2, 2026
Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
Published on: October 2, 2014
Elacestrant in ESR1-mutant, endocrine-responsive metastatic breast cancer: should health authorities consider post
C Valenza1, D Trapani1, F-C Bidard2
1Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Abstract:
For patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) metastatic breast cancer (mBC) progressed on first-line endocrine therapy plus a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i), fulvestrant, a selective estrogen receptor degrader (SERD) administered intramuscularly, represented the only monotherapy option until the approval of elacestrant. This oral SERD has been approved for patients with ESR1-mutant HR+/HER2- mBC by the European Medicines Agency, the Food and Drug Administration, and the UK Medicines and Healthcare products Regulatory Agency, according to the results of the randomized phase III EMERALD trial, which demonstrated elacestrant superiority over standard endocrine monotherapy. Consequently, elacestrant has been incorporated in the European Society for Medical Oncology and American Society of Clinical Oncology guidelines. However, in Europe, the access to this recommended drug depends on the decision of the National Health Authorities of each state. In this communication, we describe the main results and implications of the EMERALD trial, in the context of the biomarker-driven algorithm for patients with HR+/HER2- mBC progressed on CDK4/6i, and conclude that a subgroup of patients with ESR1-mutant tumors and specific clinical features can really derive a clinically meaningful benefit from elacestrant, sparing access to more toxic combination approaches and preserving the quality of life.
Insights
Elacestrant, an oral selective estrogen receptor degrader (SERD), offers a superior treatment option for patients with ESR1-mutant metastatic breast cancer (mBC) progressing on prior therapies. This advance provides a targeted therapy, improving outcomes for a specific mBC subgroup.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) often progresses on first-line endocrine therapy plus a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i).
- Fulvestrant, an intramuscular selective estrogen receptor degrader (SERD), was the sole monotherapy option for such patients before elacestrant's approval.
- Elacestrant, an oral SERD, has gained regulatory approval for specific mBC patient populations based on pivotal trial data.
Purpose of the Study:
- To evaluate the efficacy and safety of elacestrant compared to standard endocrine monotherapy in patients with HR+/HER2- mBC who progressed on CDK4/6i treatment.
- To assess elacestrant's role within a biomarker-driven treatment algorithm for advanced breast cancer.
- To highlight the clinical benefit of elacestrant in patients with ESR1-mutant tumors.
Main Methods:
- The study involved a randomized phase III trial (EMERALD) comparing elacestrant to standard endocrine monotherapy.
- Patients included had HR+/HER2- mBC with disease progression after first-line CDK4/6i and endocrine therapy.
- Genomic testing for ESR1 mutations was a key component of patient selection and analysis.
Main Results:
- Elacestrant demonstrated superiority over standard endocrine monotherapy in the overall trial population and particularly in patients with ESR1 mutations.
- The randomized phase III EMERALD trial confirmed elacestrant's efficacy in this patient subgroup.
- Elacestrant is now incorporated into major clinical guidelines, including ESMO and ASCO.
Conclusions:
- Elacestrant provides a clinically meaningful benefit for a subgroup of patients with ESR1-mutant HR+/HER2- mBC.
- This oral SERD offers a targeted approach, potentially sparing patients from more toxic combination therapies.
- Elacestrant contributes to preserving patients' quality of life while managing advanced breast cancer.
