Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): Safety analyses from the phase III EMBER-3 trial

Background: Imlunestrant is a next-generation, brain-penetrant, oral SERD. The EMBER-3 trial (NCT04975308) in patients with ER+, HER2- ABC and disease progression on/after aromatase inhibitor therapy showed significant progression-free survival improvement with imlunestrant (imlu; 400 mg once daily [QD]) over standard therapy (SOC, fulvestrant or exemestane) among patients with ESR1 mutations, as well as with imlunestrant+abemaciclib (imlu [400 mg QD] + abema [150 mg twice daily]) over imlu in all patients regardless of ESR1 mutation status. Detailed safety analyses are presented. Methods: The safety population included all patients who received at least one 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 patients: imlu (n=327), SOC (n=324), and imlu+abema (n=208). Incidence of any (imlu: 83%; SOC: 84%; imlu+abema: 98%), $ grade 3 TEAEs (imlu: 17%; SOC: 21%; imlu+abema: 49%), and serious AEs (SAEs; imlu: 10%; SOC 12%; imlu+abema: 17%) were similar between imlu and SOC arms and higher in the combination arm. Most common any-grade AEs with imlu were diarrhea (21%), nausea (17%), and fatigue (23%) and with imlu+abema were diarrhea (86%), nausea (49%), and neutropenia (48%); majority were grade 1 AEs. Incidence of elevated transaminases (any%/$G3%: 16/1 and 20/5), VTE (1/0 and 3/1), ILD (1/0 and 2/0), bradycardia (2/0 and 1/0), and photopsia (0/0 and 0/0) were relatively low or not observed with imlu and imlu+abema, respectively. Dose reduction rates were 2% with imlu and 39% with imlu+abema, and discontinuation rates due to AEs were low (4% and 6%, respectively). The table characterizes the most commonly observed AEs. Further details will be presented. Conclusions: Imlunestrant had a favorable safety profile, similar to SOC, with mostly grade 1 AEs. Safety of imlunestrant + 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, as monotherapy or in combination with abemaciclib, provides a safe, tolerable, all-oral targeted therapy option for patients with ER+, HER2- ABC. Clinical trial information: NCT04975308. Research Sponsor: Eli Lilly and Company.