FDA approves immunosuppressant Inluriyo (Imlunestrant) for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

On September 25, 2025, the Food and Drug Administration (FDA) approved imlunestrant (trade name: Inluriyo) developed by Eli Lilly and Company, an estrogen receptor antagonist specifically used to treat patients with estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative, advanced or metastatic breast cancer with estrogen receptor 1 (ESR1) mutations. These patients experience disease progression despite at least one type of endocrine therapy.

At the same time,The FDA also approved the Guardant360 CDx test as an auxiliary diagnostic tool, which can effectively identify breast cancer patients with ESR1 mutations, thus providing a basis for treatment with imlunestrant. Complete prescribing information for imlunestrant will be posted on the Drugs@FDA website for medical staff and patients to check.

Aboutimlunestrant’s efficacy and safety, EMBER-3 (NCT04975308) is an important clinical trial designed to evaluate the efficacy of this drug. This was a randomized, open-label, active-controlled, multicenter trial enrolling 874 patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer. These patients had previously been treated with an aromatase inhibitor alone or in combination with a CDK4/6 inhibitor and were excluded if they were eligible for a PARP inhibitor.

In the trial, patients were randomly assigned in a ratio of 1:1:1 to the imlunestrant group, the investigator's choice of endocrine therapy group (such as fulvestrant or exemestane), or other investigational combination regimen groups. When randomizing, factors such as previous CDK4/6 treatment, visceral metastasis, and geographical area were taken into consideration. With the Guardant360 CDx assay, the research team used analysis of circulating tumor DNA (ctDNA) to confirm the patient's ESR1 mutation status and limit ESR1 mutations within specific ligand-binding domains.

The primary efficacy outcome was investigator-assessed progression-free survival (PFS), compared using RECIST v1.1 standards, aiming to analyze the difference in efficacy between imlunestrant and the endocrine therapy selected by the investigator in patients with ESR1 mutated tumors. Other efficacy indicators include overall survival (OS) and objective response rate (ORR). In people with ESR1 mutations (n=256), the PFS of imlunestrant was significantly better than the endocrine therapy chosen by the investigators. Median PFS was 5.5 months (95% CI: 3.9-7.4) in the nonmenopausal group and 3.8 months (95% CI: 3.7-5.5) in the investigator-selected group. The hazard ratio was 0.62 (95% CI: 0.46-0.82); p-value was 0.0008. The ORR in the non-experimental arm was 14.3%, while the ORR in the investigator-selected arm was 7.7%. In the analysis of PFS, OS data are still immature, and 31% of patients in the ESR1 mutation population died.

For medication recommendations,The recommended dose of imlunestrant is 400 mg taken orally once a day. The specific taking time should be taken on an empty stomach at least 2 hours before a meal or 1 hour after a meal. Treatment should be continued until the disease worsens or unacceptable toxicity occurs. The launch of this drug provides a new treatment option for patients with advanced or metastatic breast cancer and has important clinical significance.

In terms of safety, the most common adverse events (incidence≥10%) include laboratory abnormalities, such as decreased hemoglobin, musculoskeletal pain, decreased calcium, neutropenia, increased AST, fatigue, diarrhea, increased ALT, increased triglycerides, nausea, thrombocytopenia, constipation, increased cholesterol, and abdominal pain.

References:https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-imlunestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast