The Food and Drug Administration has approved Inluriyo, or imlunestrant, in combination with Verzenio, or abemaciclib, for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer that has progressed after at least one line of endocrine therapy. The September 18 decision makes tumor testing a formal part of selecting patients for the all-oral regimen: the ESR1 mutation must be identified with an FDA-authorized test.
The approval expands the U.S. use of Inluriyo, which the FDA first approved as a single medicine for this same biomarker-defined population on September 25, 2025. It is not an approval for all people with ER-positive breast cancer or all metastatic breast cancers. The evidence cited for the new two-drug regimen comes from a smaller exploratory subgroup within a larger clinical trial, and survival results were not yet mature.
Testing determines who is eligible
Alongside the treatment decision, the FDA approved Guardant360 CDx as a companion diagnostic for identifying ESR1 mutations in patients being considered for imlunestrant plus abemaciclib. A companion diagnostic is a test specifically authorized to help determine whether a patient has the molecular feature required for a particular treatment.
ER-positive cancers use estrogen-receptor signaling to help drive growth. Imlunestrant is an endocrine therapy designed to target that receptor, while abemaciclib is a CDK4/6 inhibitor, a class of medicines used in hormone-receptor-positive advanced breast cancer. The newly authorized use is limited by several clinical features at once: estrogen-receptor positivity, HER2-negative status, an ESR1 mutation, advanced or metastatic disease, and progression after endocrine treatment.
That specificity is important because a biomarker-defined approval does not establish that the combination has the same benefit in patients whose tumors lack the mutation. The FDA said that people should be identified using an authorized test, rather than being selected solely on the basis of their cancer’s hormone-receptor status.
What the EMBER-3 trial found
The FDA based its assessment on EMBER-3, a randomized, open-label, active-controlled Phase 3 trial that enrolled 874 adults with previously treated ER-positive, HER2-negative locally advanced or metastatic breast cancer. Participants were assigned in equal proportions to imlunestrant alone, an investigator’s choice of endocrine therapy, or imlunestrant plus abemaciclib.
The numerical results supporting the combination were reported for an exploratory subgroup of 159 participants with ESR1-mutated tumors, not for all 874 people enrolled. In that subgroup, median investigator-assessed progression-free survival was 11.1 months for the combination and 5.5 months for imlunestrant alone. The estimated hazard ratio was 0.53, with a 95% confidence interval of 0.35 to 0.80.
Progression-free survival measures the time until cancer is found to have grown or spread, or until death from any cause, depending on the trial definition. In a randomized study, a difference between assigned treatment groups can support a causal interpretation within the population studied. But the subgroup was exploratory, which makes its size and status important when interpreting the estimate. It also compared the two-drug regimen with imlunestrant alone, not with the investigator’s-choice endocrine-therapy arm.
The FDA reported objective responses in 35% of patients receiving the combination and 15% of those receiving imlunestrant alone in the ESR1-mutated subgroup. Overall-survival data were immature at the interim analysis, when 35% of deaths had occurred among patients with ESR1-mutated tumors. The progression-free-survival result therefore should not be read as proof that the regimen extends overall survival.
An expansion, not a first approval
Inluriyo’s first FDA approval last year was for monotherapy after at least one line of endocrine therapy in adults with the same ER-positive, HER2-negative, ESR1-mutated advanced or metastatic disease. In the 2025 FDA decision, the agency described results from the monotherapy portion of EMBER-3.
The drug has also received European authorization. The European Medicines Agency’s public assessment report says the European Commission’s marketing authorization became valid throughout the European Union in January 2026. Regulatory decisions and approved indications can differ between the United States and Europe, so the U.S. combination authorization should not be assumed to describe availability or use elsewhere.
Eli Lilly, which makes both medicines, said in its announcement of the FDA decision that the approval would add an all-oral combination option. Lilly characterized the action as a full approval; the FDA notice confirms the approval but does not use that classification.
Safety and treatment decisions
The treatment combines two medicines with important safety considerations. The FDA lists embryo-fetal toxicity as a warning and precaution for imlunestrant. For abemaciclib, the agency lists diarrhea, neutropenia, interstitial lung disease or pneumonitis, hepatotoxicity, venous thromboembolism and embryo-fetal toxicity among warnings and precautions.
Those risks, along with previous treatments, other health conditions and the results of tumor testing, can affect whether the regimen is appropriate for an individual. People should discuss mutation testing, expected benefit, side effects and monitoring with their oncology team.
For now, the most concrete measure of benefit reported for the newly approved combination is the delay in disease progression seen in the 159-patient ESR1-mutated subgroup. Whether that difference translates into a survival advantage remains unresolved until more follow-up is available.