The EMBER-3 trial evaluated imlunestrant, a next-generation, brain-penetrant, oral selective estrogen receptor degrader, in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer (ABC) who experienced disease progression following aromatase inhibitor therapy. The study demonstrated significant progression-free survival improvement with imlunestrant monotherapy (400 mg once daily) compared with standard therapies (fulvestrant or exemestane) in patients with ESR1 mutations, and with imlunestrant combined with abemaciclib (400 mg once daily + 150 mg twice daily) in all patients regardless of ESR1 mutation status.

Safety analyses included 859 patients across 3 treatment arms: imlunestrant monotherapy (n=327), standard therapy (n=324), and imlunestrant plus abemaciclib combination (n=208). Treatment-emergent adverse events (TEAEs) were frequent, but mostly grade 1 and manageable. The incidence of TEAEs was similar between imlunestrant monotherapy and standard therapy, while higher in the combination arm. Grade ≥3 TEAEs were observed in all 3 arms, though rates of Grade ≥3 TEAEs were higher in the combination arm. The most frequent any-grade adverse events (AEs) included diarrhea, nausea, and fatigue for imlunestrant monotherapy, and diarrhea, nausea, and neutropenia for the combination therapy. Dose-reduction rates were minimal for imlunestrant monotherapy but higher for the combination therapy, and discontinuation rates due to AEs remained low across all treatment arms. Selected safety data is displayed in the Table below.

Overall, imlunestrant demonstrated a favorable safety profile comparable with standard therapy, with manageable AEs and few discontinuations. The safety of imlunestrant combined with abemaciclib aligned with known abemaciclib toxicity profiles without additive risks. These findings support imlunestrant as a safe, tolerable, and effective all-oral targeted therapy option for patients with ER-positive, HER2-negative ABC.

Source: O’Shaughnessy J, et al. Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): safety analyses from the phase III EMBER-3 trial. Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 1060.