FDA approves Inluriyo (imlunestrant) for ESR1-mutated advanced breast cancer

The U.S. Food and Drug Administration has approved Inluriyo (imlunestrant), a once-daily oral pill from Eli Lilly, for adults with estrogen receptor-positive (ER+), HER2-negative, ESR1-mutated advanced or metastatic breast cancer whose disease progressed after at least one prior line of endocrine therapy ^[1]. The drug is a 200 mg tablet taken as a 400 mg daily dose, and Lilly says it is expected to be available in U.S. pharmacies in the coming weeks ^[1].

The approval is based on the Phase 3 EMBER-3 trial, which enrolled 874 patients overall, with the ESR1-mutated group used for approval totaling 256 patients ^[1]. In that group, Inluriyo cut the risk of cancer progression or death by 38% compared with standard endocrine therapy (fulvestrant or exemestane) ^[1]. Median progression-free survival was 5.5 months on Inluriyo versus 3.8 months on the comparator therapy, a difference the trial reported as statistically significant ^[1].

ESR1 mutations arise in roughly half of patients with ER+, HER2-negative metastatic breast cancer during or after treatment with an aromatase inhibitor, according to Lilly, and these mutations are linked to resistance to standard hormone therapy ^[1]. Because Inluriyo works by binding to and helping break down the estrogen receptor even when it carries this mutation, it is designed to keep working in cases where older hormone therapies fail ^[1].

Side effects reported in the trial were mostly mild to moderate. The most common adverse reactions occurring in at least 10% of patients, including lab abnormalities, were decreased hemoglobin (30%), musculoskeletal pain (30%), decreased calcium (26%), decreased neutrophils (26%), increased AST (25%), fatigue (23%), diarrhea (22%), increased ALT (21%), increased triglycerides (21%), nausea (17%), decreased platelets (16%), constipation (10%), increased cholesterol (10%), and abdominal pain (10%) ^[1]. Serious adverse reactions occurred in 10% of patients, and fatal adverse reactions occurred in 1.8%, including cardiac arrest, heart attack, right ventricular failure, hypovolemic shock, and upper gastrointestinal bleeding, each in 0.3% of patients ^[1]. About 4.6% of patients stopped treatment permanently because of side effects ^[1].

The label carries a warning about the risk of harm to a fetus, based on animal studies, and instructs patients who can become pregnant, or their partners, to use effective contraception during treatment and for one week afterward ^[1]. Lactating patients are advised not to breastfeed during treatment and for one week after the last dose ^[1]. The drug also interacts with certain other medications processed by the liver enzyme CYP3A, and dosing may need to be adjusted for patients with moderate to severe liver impairment ^[1].

Why it matters for patients

For patients whose ER+, HER2-negative breast cancer has progressed and who test positive for an ESR1 mutation, Inluriyo offers a new oral option instead of the injectable fulvestrant or older aromatase-blocking pills like exemestane ^[1]. Because ESR1 mutations affect close to half of people who have been through hormone therapy for this cancer type, this is a fairly common situation among people whose disease has come back or progressed ^[1]. The drug does not cure the disease; in the trial it delayed progression by about six weeks on average compared with older therapy, and side effects, while mostly mild, included some serious and rare fatal events ^[1]. Whether an individual patient's tumor carries the ESR1 mutation, and whether Inluriyo is an appropriate option, is a decision that involves genetic testing and discussion with an oncologist, not something described in this release ^[1].

What happens next

Lilly says Inluriyo should reach U.S. pharmacies within weeks of the September 25, 2025 approval ^[1]. The company is also running a separate Phase 3 trial, EMBER-4, testing the same drug in earlier-stage, non-metastatic ER+, HER2-negative breast cancer in patients at higher risk of recurrence; that trial is enrolling about 8,000 patients worldwide, though no results or completion date are given in this release ^[1].