EMERALD trial - elacestrant in hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer

Endocrine therapy represents the cornerstone of treatment in hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC)

• the natural course of this disease is marked by endocrine resistance, mainly due to Estrogen Receptor 1 (ESR1) acquired mutation (1)

The EMERALD trial, was an international, open-label, randomized phase III trial that evaluated the efficacy and safety of the oral selective estrogen receptor degrader, elacestrant, versus endocrine monotherapy (standard-of-care [SOC]) in patients with previously treated estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, including patients with ESR1-mutated tumors

• elacestrant is a novel, oral selective ER degrader
• demonstrated a significant progression-free survival (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
• is suggested that this evidence provides a strong signal for role of testing in activating gain-of-function mutations in the estrogen receptor gene ligand-binding domain (ESR1 mutation) to guide therapy for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC)

Reference:

• Urso L, Vernaci G, Carlet J, Lo Mele M, Fassan M, Zulato E, Faggioni G, Menichetti A, Di Liso E, Griguolo G, Falci C, Conte P, Indraccolo S, Guarneri V, Dieci MV. ESR1 Gene Mutation in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Patients: Concordance Between Tumor Tissue and Circulating Tumor DNA Analysis. Front Oncol. 2021 Mar 11;11:625636. doi: 10.3389/fonc.2021.625636. PMID: 33777770; PMCID: PMC7991720
• Burstein HJ et al. Testing for ESR1 Mutations to Guide Therapy for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update. Journal of Clinical Oncology May 17th 2023.