The U.S. Food and Drug Administration has granted full approval to Eli Lilly’s Inluriyo, or imlunestrant, in combination with Verzenio, or abemaciclib, for adults with ER-positive, HER2-negative, ESR1-mutated locally advanced or metastatic breast cancer that has progressed after at least one line of endocrine therapy.
The treatment is limited to patients whose ESR1 mutation is identified through an FDA-authorized test. Inluriyo is an oral estrogen-receptor antagonist and Verzenio is a CDK4/6 inhibitor. The approval, announced by Lilly on Sept. 18, expands use of Inluriyo beyond its prior approval as a single-agent treatment in the same biomarker-defined metastatic setting.
The decision was based on data from the Phase 3 EMBER-3 trial. The analysis included 159 patients with ESR1-mutated metastatic breast cancer previously treated with an aromatase inhibitor, with or without a CDK4/6 inhibitor, in either adjuvant or metastatic treatment settings.
Patients received Inluriyo alone or the Inluriyo-Verzenio combination following disease progression. Median progression-free survival was 11.1 months for the combination group, compared with 5.5 months for patients receiving Inluriyo alone. The hazard ratio was 0.53, with a 95% confidence interval of 0.35 to 0.80.
ESR1 mutations can emerge during or after treatment with aromatase inhibitors and can activate estrogen receptors, contributing to tumor growth. The combination targets the estrogen receptor and cell-cycle pathways.
The Inluriyo label carries a warning and precaution for embryo-fetal toxicity. Verzenio’s label includes warnings and precautions for severe diarrhea, neutropenia, interstitial lung disease or pneumonitis, liver toxicity, venous thromboembolism, embryo-fetal toxicity and increased serum creatinine.
In the combination arm of EMBER-3, most reported adverse events were Grade 1 or Grade 2. Common reactions included decreased neutrophils, diarrhea, anemia, nausea, fatigue, infections and elevated liver enzymes.
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