FDA Approves Imlunestrant for ESR1-Mutated Advanced Breast Cancer

On September 25, 2025, the FDA approved imlunestrant (Inluriyo) for the treatment of advanced or metastatic breast cancer that is estrogen receptor (ER)-positive, HER2-negative, and ESR1-mutated. This approval is based on clinical evidence demonstrating its effectiveness in targeting ESR1 mutations, which are associated with resistance to standard endocrine therapies. Imlunestrant works by binding to estrogen receptors and promoting their degradation, thereby reducing tumor growth in patients with these specific genetic mutations. This decision provides an additional treatment option for patients with advanced breast cancer whose disease has progressed despite prior therapies.¹

This approval applies to patients with disease progression after at least 1 line of endocrine therapy. Additionally, the FDA approved the Guardant360 CDx assay as a companion diagnostic to identify ESR1 mutations in eligible patients.¹

Efficacy and Safety

The approval was based on results from the EMBER-3 trial (NCT04975308), which enrolled 874 patients previously treated with aromatase inhibitors. Key findings for the ESR1-mutated population (n=256) include:

• Progression-Free Survival (PFS): Median PFS was 5.5 months with imlunestrant versus 3.8 months with investigator’s choice of endocrine therapy (hazard ratio 0.62, P=.0008)
• Objective Response Rate (ORR): ORR was 14.3% for imlunestrant, compared with 7.7% for the investigator’s choice
• Overall Survival: Data remain immature, with 31% of deaths reported

The most common adverse events (≥10%) included decreased hemoglobin, fatigue, diarrhea, increased liver enzymes (AST/ALT), nausea, musculoskeletal pain, and other laboratory abnormalities.

Dosage Recommendation

The recommended dose of imlunestrant is 400 mg orally once daily on an empty stomach (at least 2 hours before or 1 hour after food), continued until disease progression or unacceptable toxicity.

This approval provides a new treatment option for patients with ESR1-mutated breast cancer, offering improved PFS compared with standard endocrine therapies.

Reference

1. US Food and Drug Administration. FDA approves imlunestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. Published October 2023. Accessed October 6, 2023. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-imlunestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast