FDA approves imlunestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer
Regulatory approval: On Sept 25, 2025, the FDA approved imlunestrant (Inluriyo; Eli Lilly) for adults 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 EMBER-3, where investigator-assessed median PFS in the ESR1-mutated subgroup was 5.5 vs 3.8 months versus investigator’s choice endocrine therapy (HR 0.62; p=0.0008). The FDA also approved Guardant360 CDx as a companion diagnostic.
FDA approval (Sept 25, 2025)
The US FDA approved imlunestrant (Inluriyo; Eli Lilly), an estrogen receptor antagonist, for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer whose disease has progressed after at least one line of endocrine therapy.
The FDA also approved Guardant360 CDx as a companion diagnostic to identify ESR1 mutations for treatment selection.
Supporting trial evidence: EMBER-3 (NCT04975308)
Approval was based on EMBER-3, a randomized, open-label, active-controlled, multicenter trial (N=874) enrolling patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer previously treated with an aromatase inhibitor (alone or with a CDK4/6 inhibitor). Patients eligible for a PARP inhibitor were excluded.
Patients were randomized 1:1:1 to imlunestrant, investigator’s choice endocrine therapy (fulvestrant or exemestane), or an additional investigational combination regimen. ESR1 status was determined by ctDNA using Guardant360 CDx and was limited to specific ligand-binding domain mutations.
In the ESR1-mutated subgroup (n=256), investigator-assessed PFS favored imlunestrant: median 5.5 vs 3.8 months (HR 0.62, 95% CI 0.46–0.82; p=0.0008). ORR was 14.3% vs 7.7%. OS data were immature (31% deaths at PFS analysis).
Safety and dosing (from FDA summary)
Common adverse events (≥10%), including laboratory abnormalities, included decreased hemoglobin, musculoskeletal pain, decreased calcium, decreased neutrophils, increased AST/ALT, fatigue, diarrhea, increased triglycerides/cholesterol, nausea, decreased platelets, constipation, and abdominal pain. Recommended dose: 400 mg orally once daily, taken on an empty stomach, until progression or unacceptable toxicity.