FDA approves Inluriyo combo for ESR1-mutated breast cancer

On September 18, 2026, FDA approved Inluriyo (imlunestrant) in combination with Verzenio (abemaciclib) for adults with estrogen receptor-positive (ER-positive), human epidermal growth factor receptor 2-negative (HER2-negative), advanced or metastatic breast cancer with an estrogen receptor 1 (ESR1) mutation, as detected by an FDA-authorized test. Eligible patients must have disease progression after at least one line of endocrine therapy. FDA also approved the Guardant360 CDx assay as a companion diagnostic to identify ESR1 mutations.

In the phase 3 EMBER-3 trial, adding Verzenio to Inluriyo reduced the risk of disease progression or death by 47% compared with Inluriyo alone in 159 patients with ESR1-mutated tumors. Median progression-free survival (PFS) was 11.1 months with the combination versus 5.5 months with Inluriyo alone, and the objective response rate (ORR) was 35% versus 15%. Overall survival data remain immature. Inluriyo alone did not improve PFS over investigator's choice of endocrine therapy (fulvestrant or exemestane) in the overall population or in patients without detectable ESR1 mutations, indicating that the benefit was limited to the ESR1-mutated group.

The combination's safety profile was consistent with the known effects of each drug, and most adverse events were Grade 1 to 2. Common adverse reactions included diarrhea, decreased neutrophil counts, nausea, fatigue, anemia, infections, and elevated liver enzymes. Warnings and precautions include neutropenia, interstitial lung disease or pneumonitis, hepatotoxicity, venous thromboembolism, and embryo-fetal toxicity.

The approval follows FDA's accelerated approval of Etcamah (camizestrant) with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor (abemaciclib, palbociclib, or ribociclib) for patients whose ESR1 mutation is detected before radiographic progression, an approach that still requires confirmatory evidence of clinical benefit. Inluriyo (imlunestrant) plus Verzenio (abemaciclib), by contrast, received full approval for use after progression on prior endocrine therapy. Because ESR1 mutations are a common mechanism of acquired resistance during or after aromatase inhibitor therapy, the two approvals provide biomarker-directed options at different points in the treatment continuum. They also sharpen an ongoing question in breast cancer care: whether endocrine therapy should be changed when an ESR1 mutation first emerges on circulating tumor DNA testing or after clinical progression.

“In EMBER-3, switching both the endocrine therapy and CDK 4/6 inhibitor, for the majority of patients, to imlunestrant plus abemaciclib at disease progression achieved a median progression-free survival of 11.1 months and a safety profile consistent with that of each medicine individually, establishing a meaningful new treatment option,” said Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center and principal investigator of EMBER-3.

Sources: FDA. (2026 Sep 18) FDA approves imlunestrant in combination with abemaciclib for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer; Eli Lilly and Company (2026 Sep 18) U.S. FDA approves Inluriyo (imlunestrant) in combination with Verzenio (abemaciclib) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer