Background
Imlunestrant is a next-generation, brain-penetrant, oral SERD. The EMBER-3 trial (NCT04975308) in patients with estrogen receptor–positive (ER+), HER2-negative (HER2–) advanced breast cancer and disease progression on/after aromatase inhibitor therapy showed significant PFS improvement with imlunestrant (400 mg once daily [QD]) over standard therapy (SOC, fulvestrant or exemestane) among patients with ESR1 mutations, as well as with imlunestrant (400 mg QD) plus abemaciclib (150 mg BID) over imlunestrant in all patients regardless of ESR1 mutation status. Detailed safety analyses are presented.
Methods
The safety population included all patients who received 1 or more dose of study treatment. Analyses included incidence, severity (CTCAE v 5.0), management, and outcomes of common treatment-emergent adverse events (TEAEs).
Results
Safety analyses included 859 pts: imlunestrant (n = 327), SOC (n = 324), and imlunestrant plus abemaciclib (n = 208). Incidence of any (imlunestrant: 83%; SOC: 84%; imlunestrant plus abemaciclib: 98%), grade 3 or higher TEAEs (imlunestrant: 17%; SOC: 21%; imlunestrant plus abemaciclib: 49%), and serious AEs (SAEs; imlunestrant:10%; SOC:12%; imlunestrant plus abemaciclib: 17%) were similar between imlunestrant and SOC arms and higher in the combination arm. 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%); majority were grade 1 AEs. For imlunestrant, SOC, and imlunestrant plus abemaciclib, grade 1 AEs for diarrhea were 18%, 9%, and 50% and for nausea 14%, 8%, 31%, respectively. Grade 2 AEs for diarrhea were 3%, 3%, 28% and for nausea 3%, 5%, 15%, respectively. For imlunestrant and imlunestrant plus abemaciclib, grade 3 or higher AEs for diarrhea were 0.3% and 8% and nausea 0.3% and 2%, respectively. No grade 3 or higher AEs observed in SOC group for diarrhea and nausea. Dose reduction rates were 2% with imlunestrant and 39% with imlunestrant plus abemaciclib, and discontinuation rates due to AEs were low (4% and 6%, respectively).
Conclusions
Imlunestrant had a favorable safety profile, similar to SOC, with mostly grade 1 AEs. Safety of imlunestrant plus abemaciclib was consistent with the known abemaciclib profile, without additive toxicity. AEs were manageable with supportive medications and/or dose adjustments, resulting in few discontinuations in all arms. Imlunestrant alone or with abemaciclib, provides a safe, tolerable, all-oral targeted therapy option for patients with ER+, HER2– advanced breast cancer.
Presented at American Society of Clinical Oncology - 61st Annual Meeting
