Eli Lilly and Company announced on September 25, 2025, that the U.S. Food and Drug Administration (FDA) has approved Inluriyo (imlunestrant), a 200 mg oral tablet, for the treatment of adults with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), ESR1-mutated advanced or metastatic breast cancer (MBC). This approval targets patients whose disease has progressed following at least one line of endocrine therapy (ET), addressing a critical need as approximately 50% of ER+, HER2- MBC patients develop ESR1 mutations after aromatase inhibitor exposure, leading to treatment resistance.
The approval is supported by data from the Phase 3 EMBER-3 trial, a randomized, open-label study involving 874 patients with ER+, HER2- locally advanced or MBC who had recurred or progressed after aromatase inhibitor therapy, with or without CDK4/6 inhibitors. In the ESR1-mutated subgroup (n=256), Inluriyo monotherapy demonstrated a 38% reduction in the risk of progression or death compared to investigator’s choice of ET (fulvestrant or exemestane), with a hazard ratio of 0.62 (95% CI: 0.46-0.82; p=0.0008). Median progression-free survival (PFS) was 5.5 months for Inluriyo versus 3.8 months for ET. Patients were treated in first-line MBC settings post-adjuvant AI (32%) or second-line after initial MBC therapy (64%).
Inluriyo functions as an oral estrogen receptor antagonist that binds, blocks, and degrades overactive ERs, including those with ESR1 mutations, to inhibit cancer growth. Administered as a 400 mg once-daily dose on an empty stomach, it provides a convenient, all-oral alternative to injectable therapies. The trial highlighted a tolerable safety profile: most adverse events were Grade 1-2, with common reactions including decreased hemoglobin (30%), musculoskeletal pain (30%), and others like fatigue, diarrhea, and nausea (≥10%). Serious adverse reactions occurred in 10% of patients, with 4.6% discontinuing due to AEs, 2.4% requiring dose reductions, and 10% interruptions. Warnings include embryo-fetal toxicity, advising contraception use.
Experts, including Dr. Komal Jhaveri from Memorial Sloan Kettering, emphasize Inluriyo’s role in overcoming resistance in ESR1-mutated MBC. Ongoing studies like EMBER-4 explore its adjuvant use in early breast cancer. Inluriyo is expected to launch in the U.S. soon, expanding options for metastatic breast cancer, which affects 6-10% of new diagnoses and has a 30% five-year survival rate. This approval underscores Lilly’s commitment to innovative oncology solutions amid global breast cancer’s high burden, with over 2.3 million cases annually.
