The US Food and Drug Administration approved imlunestrant (Inluriyo) with abemaciclib (Verzenio) in adults with estrogen receptor–positive, human epidermal growth factor receptor 2–negative, estrogen receptor 1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy, according to an FDA press release.
The FDA authorized use of the Guardant360 CDx assay as a companion device to detect estrogen receptor 1 (ESR1) mutations when selecting patients for the combination.
EMBER-3 included 874 adults with estrogen receptor–positive, human epidermal growth factor receptor 2–negative locally advanced or metastatic breast cancer who had previously received an aromatase inhibitor alone or with a cyclin-dependent kinase 4/6 inhibitor. The study was randomized, open label, active controlled, and multicenter. The trial excluded patients who were eligible for PARP inhibitor therapy.
Patients were randomly assigned to imlunestrant, investigator-selected endocrine therapy with fulvestrant or exemestane, or imlunestrant plus abemaciclib. Investigators used the Guardant360 CDx assay to assess circulating tumor DNA for specified ESR1 mutations within the ligand-binding domain.
The major efficacy outcome for imlunestrant plus abemaciclib was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. The comparison of progression-free survival between imlunestrant plus abemaciclib and imlunestrant monotherapy was statistically significant in the overall population. An improvement in progression-free survival was not demonstrated with imlunestrant monotherapy compared with investigator-selected endocrine therapy in the overall population or among patients without detected ESR1 mutations.
In an exploratory subgroup analysis of 159 patients with ESR1-mutated tumors, median progression-free survival was 11.1 months with imlunestrant plus abemaciclib and 5.5 months with imlunestrant alone. Objective response rates were 35% and 15%, respectively. Overall survival data were immature at the interim analysis.
Imlunestrant prescribing information includes warnings and precautions for embryo-fetal toxicity. Abemaciclib prescribing information includes warnings and precautions for diarrhea, neutropenia, interstitial lung disease or pneumonitis, hepatotoxicity, venous thromboembolism, and embryo-fetal toxicity.
Source: US Food and Drug Administration
