Key Clinical Summary:

• Design/Population: A phase 3 EMBER-3 safety analysis evaluated 859 patients with ER-positive, HER2-negative advanced breast cancer treated with imlunestrant monotherapy, standard endocrine therapy or imlunestrant plus abemaciclib.
• Key Outcomes: Any-grade adverse events were similar between imlunestrant and standard of care (83% vs 84%), but higher with the combination (98%). Grade ≥3 adverse events occurred in 17% (imlunestrant), 21% (standard of care), and 49% (combination). Common adverse events with imlunestrant were fatigue (23%), diarrhea (21%), and nausea (17%), mostly low grade. The combination increased diarrhea (86%), neutropenia (48%), and dose reductions (39% vs 2% with monotherapy), though discontinuation rates remained low (4 to 6%).
• Clinical Relevance: Imlunestrant demonstrates a favorable safety profile comparable to standard endocrine therapy, with manageable toxicity as monotherapy and in combination with abemaciclib, supporting its role as a well-tolerated, all-oral treatment option for ER-positive, HER2-negative advanced breast cancer.

Detailed safety findings from the phase 3 EMBER-3 trial further support imlunestrant, a next-generation oral selective estrogen receptor degrader, administered alone or in combination with abemaciclib among patients with ER-positive, HER2-negative advanced breast cancer.

These results were presented at the Hematology/Oncology Pharmacy Association (HOPA) Annual Meeting in New Orleans, Louisiana, by Emily Barrett, MSc, Eli Lilly and Company, Indianapolis, Indianna. 

In this study, 859 patients who experienced disease progression on or after aromatase inhibitor therapy received imlunestrant either alone (n = 327) or in combination with abemaciclib (n = 208) or standard fulvestrant or exemestane (n = 324). Safety was assessed in patient swho received ≥1 dose. 

At analysis, the incidence of any adverse event was 83% in the imlunestrant monotherapy arm, 84% in the standard arm, and 98% in the imlunestrant plus abemaciclib arm. Grade ≥3 treatment-emergent adverse events were reported in 17% of patients in the imlunestrant monotherapy arm, 21% of patients in the standard arm, and 49% of patients in the imlunestrant plus abemaciclib arm. Serious adverse events were reported in 10%, 12%, and 17% of patients, respectively. 

The most frequently reported any-grade adverse events (mainly grade 1) were fatigue (23%), diarrhea (21%), and nausea (17%) in the imlunestrant monotherapy arm and diarrhea (86%), nausea (49%), and neutropenia (48%) in the imlunestrant plus abemaciclib arm. Grade ≥3 diarrhea was reported in 0.3% of patients in the imlunestrant monotherapy arm and 8% of patients in the imlunestrant plus abemaciclib arm. Grade ≥3 nausea was reported in 0.3% and 2% of patients, respectively. 

Dose reductions were required in 2% of patients receiving imlunestrant monotherapy and 39% of patients receiving imlunestrant plus abemaciclib. While discontinuations due to adverse events remained low, most adverse events were managed effectively with supportive care and dose modifications. 

As Dr Barrett concluded, “imlunestrant alone or with abemaciclib provides a safe, tolerable, all-oral targeted therapy option for patients with ER-positive, HER2-negative advanced breast cancer.”

Source:

Barrett E. Imlunestrant with or without abemaciclib in advanced breast cancer: Safety analyses from the phase 3 EMBER-3 trial. Presented at HOPA Annual Conference. March 25-27, 2026. CR11.