Aims: We provide evidence-based management strategies for adjuvant abemaciclib + endocrine therapy (ET) in node-positive, high-risk HR+, HER2- early breast cancer (EBC).
Methods: Data from eligible patients treated with abemaciclib from the phase 3 monarchE and phase 2 TRADE studies were summarized and supported by real-world data.
Results: Abemaciclib demonstrated a manageable safety profile across trials. In monarchE, the most frequent any-grade adverse events (AEs) in abemaciclib + ET arm were diarrhea, neutropenia, and fatigue, with a higher incidence of grade ≥3 AEs vs 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 antidiarrheal medications (79% of patients) and dose modifications (<25%). 5% of patients discontinued due to diarrhea. High estimated 4-year IDFS rates of 87%/86%/84% with abemaciclib dose intensities of ≤66%/66–93%/≥93%, respectively, indicated that efficacy was not negatively impacted by dose reductions. Seven-year monarchE data confirmed the known safety profile of abemaciclib. In TRADE, a dose-escalation approach was utilized: abemaciclib 50mg twice daily (BID) on days 1-14, 100mg BID on days 15-28 and 150mg BID thereafter. This strategy allowed more patients to reach and maintain abemaciclib 150mg BID at 12 weeks (71%) vs monarchE (~60%) and discontinuation was infrequent (7%). These results are supported by real-world data in EBC from the US, demonstrating improved abemaciclib persistence with dose reductions.
Conclusions: Abemaciclib-associated AEs are manageable through dose modifications without compromising efficacy, allowing patients to continue treatment and maximize the benefit of abemaciclib treatment.