FDA Approves Imlunestrant Plus Abemaciclib for ESR1-Mutated, ER-Positive, HER2-Negative Advanced Breast Cancer

The FDA has approved imlunestrant (Inluriyo) in combination with abemaciclib (Verzenio) for adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer whose disease has progressed following at least 1 line of endocrine therapy.

The September 18, 2026, approval applies to patients whose ESR1 mutation is identified using an FDA-authorized test. The FDA also approved the Guardant360 CDx assay as a companion diagnostic for identifying patients with breast cancer who may be eligible for treatment with the combination.

Both imlunestrant and abemaciclib are manufactured by Eli Lilly and Company.

Efficacy in the EMBER-3 Trial

The approval was supported by findings from EMBER-3 (NCT04975308), a randomized, open-label, active-controlled, multicenter trial that enrolled 874 adults with ER-positive, HER2-negative locally advanced or metastatic breast cancer previously treated with an aromatase inhibitor, either alone or in combination with a CDK4/6 inhibitor. Patients who were eligible to receive a PARP inhibitor were excluded.

Patients were randomized to receive imlunestrant alone, investigator's choice of endocrine therapy (fulvestrant or exemestane), or imlunestrant plus abemaciclib. Randomization was stratified according to previous CDK4/6 inhibitor treatment, presence of visceral metastases and geographic region. ESR1 mutation status was determined using circulating tumor DNA from blood with the Guardant360 CDx assay.

The primary efficacy measure for the combination was investigator-assessed progression-free survival (PFS) according to RECIST v1.1.

In an exploratory subgroup analysis of 159 patients with ESR1-mutated tumors, median PFS was 11.1 months with imlunestrant plus abemaciclib compared with 5.5 months with imlunestrant alone. The PFS hazard ratio was 0.53 (95% CI, 0.35-0.80).

The objective response rate (ORR) was 35% with the combination compared with 15% with imlunestrant alone. At the time of the interim analysis, overall survival data were immature, with 35% of deaths reported among patients with ESR1-mutated tumors.

The FDA noted that although the PFS comparison between imlunestrant plus abemaciclib and imlunestrant alone was statistically significant in the overall population, the observed benefit was in the ESR1-mutated population.

Dosing and Administration

The recommended dosage of imlunestrant is 400 mg orally once daily on an empty stomach, taken at least 2 hours before food or 1 hour after food.

When administered in combination with imlunestrant, the recommended dosage of abemaciclib is 150 mg orally twice daily, with or without food. Treatment should continue until disease progression or unacceptable toxicity.

The imlunestrant prescribing information includes warnings and precautions regarding embryo-fetal toxicity. The abemaciclib prescribing information includes warnings and precautions for diarrhea, neutropenia, interstitial lung disease or pneumonitis, hepatotoxicity, venous thromboembolism and embryo-fetal toxicity.

Considerations for Oncology Nurses

The approval adds an all-oral treatment option for a biomarker-defined population of patients with advanced or metastatic ER-positive, HER2-negative breast cancer. Identifying the ESR1 mutation is an important component of treatment selection, making appropriate biomarker testing and interpretation relevant to the care team.

Nurses caring for patients receiving the combination should be familiar with the administration requirements for both oral therapies and monitor patients for toxicities associated with each agent. In particular, diarrhea and neutropenia are established safety concerns with abemaciclib, while hepatotoxicity, interstitial lung disease or pneumonitis and venous thromboembolism also require attention.

Patient education around adherence to oral therapy, recognition of concerning adverse effects and when to contact the care team is also an important part of supportive care.

The FDA's approval provides another treatment approach for patients with ESR1-mutated, ER-positive, HER2-negative advanced or metastatic breast cancer following progression on endocrine therapy.

References

1. U.S. Food and Drug Administration. “FDA Approves Imlunestrant in Combination With Abemaciclib for ER-Positive, HER2-Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer.” Sept. 18, 2026.