Presenting Author: Emily Barrett, MSc, Eli Lilly and Company, Indianapolis, IN
BACKGROUND: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen receptor degrader. The EMBER-3 trial (NCT04975308) in patients with ER-positive, HER2-negative advanced breast cancer and disease progression on or after aromatase inhibitor therapy showed significant improvement in progression-free survival with imlunestrant (400 mg once daily) over standard of care (SOC; fulvestrant or exemestane) among patients with ESR1 mutations, as well as with imlunestrant (400 mg once daily) plus abemaciclib (150 mg twice daily) over imlunestrant in all patients, regardless of ESR1 mutation status.1 The detailed safety analyses are presented.
OBJECTIVES: To characterize the incidence, timing, duration, and management of the most common treatment-emergent adverse events (TEAEs) of imlunestrant monotherapy and in combination with abemaciclib in the EMBER-3 trial and to assess the safety profile of imlunestrant in different age-groups.
METHODS: The safety population included all patients who received ≥1 dose of study treatment. Analyses included the incidence, severity (Common Terminology Criteria for Adverse Events, version 5.0), management, and outcomes of common TEAEs.
RESULTS: The safety analyses included 859 patients who received imlunestrant (n=327), SOC (n=324), or imlunestrant plus abemaciclib (n=208). The incidence of any AEs (imlunestrant, 83%; SOC, 84%; imlunestrant plus abemaciclib, 98%), grade ≥3 TEAEs (imlunestrant, 17%; SOC, 21%; imlunestrant plus abemaciclib, 49%), and serious AEs (imlunestrant, 10%; SOC, 12%; imlunestrant plus abemaciclib, 17%) was similar between the imlunestrant and SOC arms and was higher in the combination arm. The most common any-grade AEs with imlunestrant were diarrhea (21%), nausea (17%), and fatigue (23%), and with imlunestrant plus abemaciclib were diarrhea (86%), nausea (49%), and neutropenia (48%); most of the AEs were grade 1. Of the imlunestrant, SOC, and imlunestrant plus abemaciclib groups, 18%, 9%, and 50%, respectively, had grade 1 diarrhea, and 14%, 8%, and 31%, respectively, had grade 1 nausea. Of these groups, 3%, 3%, and 28%, respectively, had grade 2 diarrhea, and 3%, 5%, and 15%, respectively, had grade 2 nausea. In the imlunestrant and imlunestrant plus abemaciclib cohorts, 0.3% and 8%, respectively, had grade ≥3 diarrhea and 0.3% and 2%, respectively, had grade ≥3 nausea. There were no cases of grade ≥3 diarrhea or nausea in the SOC group. The dose reduction rates were 2% with imlunestrant and 39% with imlunestrant plus abemaciclib, and the discontinuation rates as a result of AEs were low (4% and 6%, respectively).
CONCLUSION: Imlunestrant had a favorable safety profile, similar to SOC, with predominantly grade 1 AEs. The safety of imlunestrant plus abemaciclib was consistent with the known abemaciclib profile, without additive AEs. The AEs were manageable with supportive medications and/or dose adjustments, resulting in few treatment discontinuations in all arms. Imlunestrant alone or with abemaciclib provides a safe, tolerable, all-oral targeted therapy option for patients with ER-positive, HER2-negative advanced breast cancer.
- Jhaveri K, Neven P, Casalnuovo ML, et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2-advanced breast cancer (ABC), pretreated with endocrine therapy (ET): results of the phase 3 EMBER-3 trial. Clin Cancer Res. 2025;31(12 suppl):Abstract GS1-01.