FDA Approves Imlunestrant, Abemaciclib Combo for ESR1+ Metastatic Breast Cancer

The FDA has granted full approval to imlunestrant (Inluriyo; Eli Lilly and Company) in combination with abemaciclib (Verzenio; Eli Lilly and Company) for adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated locally advanced or metastatic breast cancer (MBC) whose disease progressed on at least 1 line of endocrine therapy, with the mutation confirmed by an FDA-authorized test. The approval was announced in a news release from Eli Lilly and Company.¹

For pharmacists supporting oncology patients, the combination now becomes a standard switch option once ER+ and HER2– disease develops an ESR1 mutation and progresses past initial hormone-blocking therapy.¹

EMBER-3 Data Driving the Approval

The approval rests on the phase 3 EMBER-3 trial (NCT04975308), which randomly assigned 874 patients with ER+, HER2– advanced or metastatic breast cancer to imlunestrant, investigator's choice endocrine therapy, or imlunestrant plus abemaciclib after prior aromatase inhibitor therapy with or without a CDK4/6 inhibitor. The FDA based this expanded approval on an exploratory subgroup of 159 patients with ESR1-mutated tumors who switched therapy at clinical progression: 67 received the combination and 92 received imlunestrant alone. Median progression-free survival (PFS) was about 11.1 months with the combination versus 5.5 months with imlunestrant alone (hazard ratio [HR], 0.53; 95% CI, 0.35-0.80).^1-3

That switching benefit builds on EMBER-3's original findings, published in the New England Journal of Medicine. Among 256 patients with ESR1 mutations randomized between imlunestrant and standard endocrine therapy, median PFS was about 5.5 months with imlunestrant versus 3.8 months with standard therapy. Imlunestrant did not significantly improve PFS over standard therapy in the overall 874-patient population (5.6 vs 5.5 months; HR, 0.87; 95% CI, 0.72-1.04; P = .12). But among 426 patients who were concurrently randomized, adding abemaciclib to imlunestrant improved median PFS to 9.4 months versus 5.5 months with imlunestrant alone (HR, 0.57; 95% CI, 0.44-0.73; P < .001), regardless of ESR1 status.²

This is the second FDA approval for imlunestrant in under a year. The FDA first approved it as monotherapy in September 2025 for the same ESR1-mutated population.^1,4

Safety and Monitoring

Most adverse events (AEs) with the combination were grade 1 or 2. Diarrhea occurred in approximately 86% of patients (grade 3/4: 9%), and decreased neutrophil counts occurred in 86% (grade 3/4: 21%). Alanine and aspartate aminotransferase increases occurred in 33% and 36% of patients, respectively. Serious AEs occurred in 21% of patients on the combination, and fatal AEs occurred in 3.8%, most commonly pneumonia. Among patients on the combination, 1% discontinued imlunestrant alone and 3.4% discontinued abemaciclib alone because of AEs.¹

Neither drug carries a boxed warning. The combination doesn't add new monitoring beyond what's already recommended for each agent individually: complete blood counts and liver function tests at the intervals in abemaciclib's label, plus a non–creatinine-based renal function measure, such as blood urea nitrogen, cystatin C, or calculated glomerular filtration rate, since abemaciclib can raise serum creatinine without affecting true renal function.¹

Dispensing and Counseling Considerations

Imlunestrant is dosed as 400 mg (two 200-mg tablets) once daily on an empty stomach, at least 2 hours before or 1 hour after food, whereas abemaciclib is taken twice daily at doses ranging from 50 mg to 200 mg. That mismatch in dosing frequency and food requirements is worth flagging at counseling, given that adherence errors are more likely to occur when 2 oral oncolytics on the same regimen follow different rules.

Pharmacists should also counsel on antidiarrheal readiness at the first sign of loose stools and on contraception: patients should use effective contraception during treatment and for 3 weeks after the last abemaciclib dose or 1 week after the last imlunestrant dose, whichever is longer. Imlunestrant inhibits P-glycoprotein and breast cancer resistance protein, so pharmacists should screen for substrates of those transporters, and both drugs require dose adjustment or avoidance with strong CYP3A inhibitors or inducers.¹

Lilly's ongoing phase 3 EMBER-4 trial, enrolling more than 8000 patients in the adjuvant early breast cancer setting, is expected to report initial results in 2027 and could further expand Imulunestrant’s role in ER+, HER2– breast cancer.¹

REFERENCES

1. Eli Lilly and Company. U.S. FDA approves Inluriyo (imlunestrant) in combination with Verzenio (abemaciclib) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer. News release. September 18, 2026. Accessed September 21, 2026. https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-inluriyo-imlunestrant-combination-verzenio

2. Jhaveri KL, Neven P, Casalnuovo ML, et al; EMBER-3 Study Group. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med. 2025;392(12):1189-1202. doi:10.1056/NEJMoa2410858

3. Targeted Oncology Staff. FDA approves imlunestrant plus abemaciclib in ESR1-mutated breast cancer. Targeted Oncology. September 18, 2026. Accessed September 21, 2026. https://www.targetedonc.com/view/fda-approves-imlunestrant-abemaciclib-esr1-mutated-breast-cancer

4. McGovern G. FDA approves imlunestrant tablets for ER+, HER2-, ESR1- mutated advanced or metastatic breast cancer. Pharmacy Times. September 25, 2025. Accessed September 21, 2026. https://www.pharmacytimes.com/view/fda-approves-imlunestrant-tablets-for-er-her2-esr1-mutated-advanced-or-metastatic-breast-cancer