Background: Adjuvant abemaciclib (a CDK4 & 6 inhibitor) combined with ET demonstrated a sustained benefit in invasive disease-free survival (IDFS) and a tolerable safety profile in patients (pts) with HR+, HER2-, node-positive, high-risk EBC. Almost half of the newly diagnosed breast cancers occur in women older than 65 years. Older pts often have a higher incidence of comorbidities and increased risk for toxicities. Here, we report efficacy and safety by age subgroups in monarchE to help guide management of older pts receiving adjuvant abemaciclib. Methods: Pts were randomized (1:1) to receive ET for up to 10 years +/- abemaciclib for 2 years (study treatment period). Efficacy in IDFS and distant relapse-free survival (DRFS) was assessed in the intent-to-treat population by the pre-specified age groups of <65 and ≥65 years, with hazard ratios (HR) estimated using unstratified Cox proportional hazard model within each subgroup. Safety was evaluated among older pts (≥65 years) in two subgroups; 65-74 and ≥75 years. Results: In monarchE (NCT03155997), 4787 pts (84.9%) were aged <65 years and 850 pts (15.1%) were ≥65 years. At median follow-up of 42 months, a numerically favorable IDFS effect was observed in both the <65 (270 vs 414 events; HR = 0.646, 95% CI: 0.554, 0.753) and ≥65 (66 vs 85 events; HR = 0.767, 95% CI: 0.556, 1.059) groups for abemaciclib + ET vs ET alone. Similar findings were observed in DRFS. Older pts (≥65 years) had ~5% higher incidence of grade ≥3 adverse events (AEs) than younger pts, mainly diarrhea and fatigue. Neutropenia was not increased among older pts and similarly, venous thromboembolic events occurred at similar rates (≥65 years, 3.0%; <65 years, 2.5%). Serious AEs (SAEs) and treatment discontinuations due to AEs were more common in older pts. Older pts required more dose reductions to manage AEs. Conclusions: In pts with high-risk EBC, adjuvant abemaciclib + ET showed treatment benefit across age subgroups with a manageable safety profile. Older pts did have higher rates of AEs and discontinuations, especially those older than 75 years, suggesting that more frequent surveillance with early intervention may be key to the management of these pts. Clinical trial information: NCT03155997.

*Diarrhea grade 2 for abemaciclib + ET: <65, 31%; 65-74, 31%; ≥75, 25%.