FDA Approves Imlunestrant in ESR1+ HR+, HER2- Metastatic Breast Cancer

The FDA has approved imlunestrant based on results from EMBER-3.

The FDA granted approval to imlunestrant (Inluriyo) for use in adult patients with estrogen receptor (ER)-positive, HER2-negative advanced or metastatic breast cancer with ESR1 mutations whose disease progressed following 1 or more lines of endocrine therapy, according to a news release from Eli Lilly and Company, the developer of imlunestrant.¹

The oral ER antagonist’s approval is based on data on patients with ESR1 mutations in the phase 3 EMBER-3 trial (NCT04975308), which demonstrated that imlunestrant reduced the risk of disease progression or death by 38% vs endocrine therapy. Imlunestrant had a median progression-free survival (PFS) of 5.5 months vs 3.8 months for patients receiving endocrine therapy (HR, 0.62 [95% CI, 0.46-0.82]; P = .0008).

Patients included in the trial (n = 256) were given either imlunestrant or endocrine therapy in one of two contexts:

• as a frontline therapy for metastatic disease after recurrence on adjuvant aromatase inhibitor with or without CDK4/6 inhibitor (21%)
• or, as a second-line treatment for metastatic disease after progression on an aromatase inhibitor with or without previous treatment with a CDK4/6 inhibitor (79%).

This approval marks imlunestrant’s first FDA OK. The ER antagonist is available in 200-mg tablets and is recommended as a once-daily dose of 400 mg taken orally on an empty stomach, meaning patients should take it 2 or more hours before food or 1 hour after.

What Should Nurses Know About Imlunestrant?

Changes to complete blood counts were commonly reported in patients taking imlunestrant. The most frequently observed adverse effects (AEs) in those receiving imlunestrant, occurring in at least 10% of patients, included decreased hemoglobin (30%), musculoskeletal pain (30%), hypocalcemia (26%), neutropenia (26%), elevated AST (25%), fatigue (23%), diarrhea (22%), elevated ALT (21%), hypertriglyceridemia (21%), nausea (17%), thrombocytopenia (16%), constipation (10%), elevated cholesterol (10%), and abdominal pain (10%).

Serious AEs were reported in 10% of patients. The only serious AE reported in more than 1% of patients was pleural effusion (1.2%).

Fatal AEs occurred in 1.8% of patients; causes included cardiac arrest, acute myocardial infarction, right ventricular failure, hypovolemic shock, and upper gastrointestinal hemorrhage. Each fatal AE occurred in .3% of patients.

Because imlunestrant is a CYP3A substrate, concomitant use of imlunestrant with a strong CYP3A inhibitor should be avoided when possible. In cases where this is not possible, the dose of imlunestrant should be reduced. Patients with moderate or severe hepatic impairment should also receive decreased doses.

The label for imlunestrant includes warnings that patients should not breastfeed when receiving imlunestrant and that embryo-fetal toxicitity is also possible during treatment. Contraception should be used during treatment and for 1 week after the last dose of imlunestrant.

What’s Next for Imlunestrant?

Imlunestrant is being actively investigated vs standard hormone therapy in patients with early ER-positive, HER2-negative breast cancer following treatment with endocrine therapy for 2 to 5 years and a higher-than-average risk of recurrence in the phase 3 EMBER-4 trial (NCT05514054).² EMBER-4 is active and recruiting.²

Imlunestrant’s phase 1 EMBER trial (NCT04188548), which investigated its safety and efficacy in breast and endometrial cancers, is still ongoing but is no longer recruiting.³ EMBER-3 is also ongoing.¹

Prior to imlunestrant’s approval, elacestrant (Orserdu) was the only FDA-approved therapy for patients with ESR1-mutated breast cancer. Elacestrant was approved on January 23, 2023 for use in postmenopausal female patients and adult male patients with ER-positive, HER2-negative advanced or metastatic breast cancer harboring ESR1 mutation following progression after 1 or more prior lines of endocrine therapy.⁴

References

1. U.S. FDA approves Inluriyo (imlunestrant) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer. Eli Lilly and Company. News release. September 25, 2025. Accessed September 25, 2025. https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-inluriyo-imlunestrant-adults-er-her2-esr1
2. A Study of Imlunestrant Versus Standard Endocrine Therapy in Participants With Early Breast Cancer (EMBER-4). ClinicalTrials.gov. August 24, 2022. Updated September 23, 2025. Accessed September 25, 2025. https://clinicaltrials.gov/study/NCT05514054
3. A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer (EMBER). ClinicalTrials.gov. December 6, 2019. Updated June 4, 2025. Accessed September 25, 2025. https://www.clinicaltrials.gov/study/NCT04188548
4. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. FDA. January 23, 2023. Accessed September 25, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-elacestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast-cancer