FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer
Regulatory approval: On Jan 27, 2023, the FDA approved elacestrant (Orserdu) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer after progression on at least one line of endocrine therapy. Approval was supported by the randomized EMERALD trial, which showed a progression-free survival benefit in the ESR1-mutated subgroup. The FDA also approved Guardant360 CDx as a companion diagnostic to identify eligible patients.
FDA approval (Jan 27, 2023): elacestrant for ESR1-mutated ER+/HER2− advanced/metastatic breast cancer
The FDA approved elacestrant (Orserdu; Stemline Therapeutics, Inc.) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer whose disease has progressed following at least one line of endocrine therapy. The FDA also approved Guardant360 CDx as a companion diagnostic to identify patients for treatment.
Approval was supported by EMERALD (NCT03778931), a randomized, open-label, active-controlled, multicenter trial (N=478) in which 228 patients had ESR1 mutations. Patients had progressed on 1–2 prior endocrine therapy lines, including one CDK4/6 inhibitor–containing line; up to one prior chemotherapy line in the advanced/metastatic setting was allowed. Patients were randomized 1:1 to elacestrant 345 mg orally once daily vs investigator’s choice endocrine therapy (fulvestrant or aromatase inhibitor). ESR1 status was determined in blood ctDNA using Guardant360 CDx and was limited to ESR1 ligand-binding domain missense mutations.
Primary endpoint was PFS by blinded independent review. In the ESR1-mutated subgroup, median PFS was 3.8 vs 1.9 months (HR 0.55, 95% CI 0.39–0.77; p=0.0005). An exploratory analysis in patients without ESR1 mutations showed HR 0.86 (95% CI 0.63–1.19).
Common adverse events (≥10%) included musculoskeletal pain, nausea, fatigue, vomiting, lab abnormalities (e.g., increased cholesterol, AST/ALT, triglycerides), and GI symptoms. Recommended dose: 345 mg with food once daily until progression or unacceptable toxicity.