Background
Adjuvant endocrine therapy (ET) is the standard of care (SOC) for treating estrogen receptor–positive (ER+)/HER2-negative (HER2–) early breast cancer. Despite advances to optimize adjuvant treatment in high-risk ER+/HER2– early breast cancer, there continues to be risk of local and metastatic recurrence that persists, and new therapies with desirable safety profiles are warranted. Elacestrant is a next-generation oral SERD that provides a novel mechanism of action that has shown both SERD (degradative) and SERM (partial agonist) activity that differs from currently available adjuvant ET. In the EMERALD trial, elacestrant significantly prolonged progression-free survival (PFS) vs SOC ET in the overall population (HR, 0.70; 95% CI, 0.55-0.88; P = .0018) and in patients with ESR1-mutated tumors (HR, 0.55; 95% CI, 0.39-0.77; P = .0005). In patients with ESR1-mutated tumors who received prior ET plus CDK4/6 inhibitor (CDK4/6i) 12 months or more, median PFS with elacestrant was 8.6 vs 1.9 months with SOC ET. In patients with ER+/HER2− early breast cancer, the SOLTI-1905-ELIPSE and SOLTI-2104-PremiERe trials showed that preoperative elacestrant was associated with a statistically significant mean change of complete cell cycle arrest rate and led to a shift in tumor biology toward a more endocrine-sensitive and less proliferative tumor phenotype in both pre- and post-menopausal women. Given that elacestrant demonstrated efficacy in metastatic breast cancer regardless of ESR1 mutation status relative to SOC ET and has shown biologic activity in early breast cancer, it is hypothesized that elacestrant can prolong invasive breast cancer-free survival (IBCFS) in patients with high-risk early breast cancer who received prior adjuvant ET with or without CDK4/6i.
Design and Methods
ELEGANT (NCT06492616) is a global, multicenter, open-label phase 3 study designed to evaluate elacestrant vs SOC ET (aromatase inhibitor or tamoxifen) in patients with early breast cancer and high risk of recurrence. Patients will be randomly assigned 1:1 to continue SOC ET or to elacestrant for a duration of 5 years. Eligible patients are women or men with ER+/HER2− node-positive early breast cancer who received between 2 to 5 years of SOC ET with or without CDK4/6i and have ECOG performance status of at least 1. Patients who received a prior CDK4/6i or PARP inhibitor must have already completed or discontinued these treatments. Pre/perimenopausal women and men will be administered a LHRH agonist. Exclusion criteria include stage IV metastatic breast cancer, inflammatory breast cancer, history of prior invasive breast cancer, history of malignancy within 3 years of randomization date, more than 6 months of continuous interruption of prior SOC adjuvant ET or discontinuation of adjuvant ET more than 6 months of prior to randomization, and received prior treatment with SERDs. The primary objective is IBCFS. Key secondary objectives include distant relapse-free survival, overall survival, invasive disease-free survival, safety, patient-reported outcomes-quality of life, and pharmacokinetics.
Status
Planned enrollment is 4220 patients; recruitment is ongoing.
