Early toxicity–driven dose modification and efficacy of adjuvant abemaciclib in high-risk HR+/HER2− early breast cancer: A real-world study in Chinese patients.

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Background: Adjuvant abemaciclib plus endocrine therapy (ET) improves invasive disease-free survival (iDFS) in patients with high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) early breast cancer (EBC). However, Chinese patients were underrepresented in pivotal trials, and real-world evidence regarding toxicity-driven dose management and its impact on efficacy remains limited. Methods: This single-center retrospective cohort study included 130 consecutive female patients with high-risk HR+/HER2− EBC treated with adjuvant abemaciclib plus ET between December 2021 and June 2025. High-risk status was defined by Monarch-E criteria combined with real-world clinical assessment, including multigene expression assay results used to inform recurrence risk in patients not strictly meeting pathological criteria. The primary endpoint was iDFS. Secondary endpoints included overall survival (OS), safety, and dose modification patterns. Survival outcomes were estimated using the Kaplan–Meier method and Cox proportional hazards models. Results: After a median follow-up of 24.6 months, 21 iDFS events and 1 death were observed. Dose modification occurred in 28.5% of patients, with 70.3% of initial modifications occurring within the first 3 months. Most dose reductions followed a stepwise strategy to 100 mg twice daily (78.4%) and were primarily driven by adverse events, particularly diarrhea (53.1%), of which 82.4% were grade 3. Grade ≥3 diarrhea occurred in 25.0% of patients, and interstitial lung disease in 5.7%, which may reflect intensive real-world safety monitoring and broader diagnostic capture compared with clinical trial settings. Median iDFS was 27.5 months in the dose modification group (n=37) vs. 22.7 months in the non-modification group (n=93) (log-rank test, P =0.88), confirming no efficacy compromise from early toxicity-driven dose adjustment despite limited events. Neither lymph node burden nor Ki-67 expression showed independent prognostic significance for iDFS in univariate or multivariate analyses within this cohort (all P >0.05). Conclusions: In this real-world Chinese cohort, early toxicity-driven dose modification of adjuvant abemaciclib was not associated with inferior iDFS within the current follow-up period, supporting proactive dose management rather than treatment discontinuation. Traditional clinicopathological high-risk factors did not demonstrate independent prognostic significance, potentially due to limited sample size and events. No new safety signals were identified in this study, however, the management of diarrhea and interstitial pneumonia requires further optimization in the Chinese population.