Background
Patients with node-positive, high-risk hormone receptor–positive (HR+), HER2-negative (HER2–) early breast cancer have substantial recurrence risk. Abemaciclib plus endocrine therapy (ET) is recommended for these patients based on improved invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and overall survival in monarchE. Although abemaciclib-based therapy is effective, its optimal use requires adequate tolerability management to support consistent treatment adherence. Knowledge of approaches to manage tolerability is essential but data informing effective management are spread across sources.
Objective
To inform clinical practice by providing evidence-based management strategies for adjuvant abemaciclib plus ET in early breast cancer.
Methods
Data from patients with HR+, HER2− early breast cancer treated with abemaciclib from the phase 3 monarchE (NCT03155997) and phase 2 TRADE (NCT06001762) studies were summarized and supported by real-world data.
Results
Abemaciclib has demonstrated a predictable, manageable safety profile across trials. In monarchE, the most frequent any-grade adverse events (AEs) in patients receiving abemaciclib plus ET were diarrhea, neutropenia, and fatigue, with a higher incidence of grade 3 or higher AEs than for ET alone (50% vs 17%). Overall, 84% of patients receiving abemaciclib reported diarrhea, typically low grade with early onset (median 8 days), and incidence decreased over time. At 27 months median follow-up, diarrhea was effectively managed, with 79% of patients having received antidiarrheal medications, less than 25% having a dose modification, and 5% discontinuing treatment due to diarrhea. High estimated 4-year iDFS rates of 87%, 86%, and 84% with abemaciclib dose intensities of 66% or less, 66% to 93%, and 93% or more, respectively, indicated that efficacy was not negatively impacted by dose reductions. Further, in a time-dependent Cox proportional hazard model in monarchE, iDFS and DRFS with abemaciclib were consistent at full dose vs lower doses. Seven-year monarchE data confirmed the known safety profile of abemaciclib, with no new safety signals.
In TRADE, a dose-escalation approach was utilized: patients received abemaciclib 50 mg twice daily (BID) on days 1 to 14, 100 mg BID on days 15 to 28, and 150 mg BID thereafter. This strategy allowed more patients to reach and maintain abemaciclib 150 mg BID at 12 weeks (71%) compared with monarchE (~60%) and discontinuation was infrequent (7%). These results are supported by real-world data in early breast cancer from the US, demonstrating improved abemaciclib persistence with dose reductions (increasing from 88% persisting > 3 months to 93%), and most patients who discontinued had not had prior dose modifications (70%).
Conclusion
Abemaciclib-associated AEs are manageable through dose modifications, without comprising efficacy, allowing patients to remain on treatment and maximize the benefit of abemaciclib treatment. Expert-informed guidance regarding management of AEs in patients with high-risk HR+, HER2− early breast cancer treated with abemaciclib will be presented.
