Real-World Outcomes of Abemaciclib Dose-Escalation Strategy in High-Risk Early Breast Cancer.

[INTRODUCTION] Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, is approved as adjuvant therapy for patients with node-positive, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), high-risk early breast cancer (EBC). In the monarchE trial, abemaciclib combined with endocrine therapy (ET) demonstrated a sustained invasive disease-free survival (iDFS) benefit, with absolute gains of 3.5% at 2 years, 6.4% at 4 years, and 7.6% at 5 years compared with ET alone. However, tolerability remains a major challenge. In monarchE, 16.6% of patients discontinued abemaciclib due to adverse events (AEs), 56.9% required dose interruptions, and 41.2% required dose reductions.

[OBJECTIVE] To evaluate whether a dose-escalation (DE) strategy for abemaciclib improves tolerability and reduces dose modifications compared with standard dosing (SD) in a real-world cohort.

[PATIENTS AND METHODS] We conducted a retrospective cohort study at The University of Kansas Health System, including 164 patients with HR+, HER2-, node-positive, high-risk EBC treated with adjuvant abemaciclib plus ET between October 2021 and June 2024. Patients received either DE (initiated at 50 mg or 100 mg twice daily [BID] with subsequent titration to full dose; n = 83) or SD (150 mg BID; n = 81) at provider discretion. Baseline demographics, dose modifications, discontinuations, and AEs were collected from the medical record. Outcomes were compared using chi-square tests.

[RESULTS] In the DE group, 48% of patients achieved full dose, with a median titration time of 46 days (range, 21-165). Discontinuation rates were numerically lower with DE (18% vs. 27%, P = .139), with median time to discontinuation of 80 versus 66 days. Dose interruptions occurred significantly less frequently with DE (25% vs. 65%, P = .001), as did dose reductions (14% vs. 43%, P = .001). The median duration of therapy was 107 days in the DE group and 196 days in the SD group. The most common reasons for discontinuation were diarrhea (SD 15%, DE 6%) and fatigue (SD 7%, DE 6%). The leading AEs prompting dose modifications were diarrhea (SD 38%, DE 9%, P = .001), nausea (SD 12%, DE 1%, P = .005), and fatigue (SD 12%, DE 5%, P = .094). Four patients in the SD group successfully reinitiated abemaciclib using a DE approach after a median treatment hold of 6 months.

[CONCLUSION] A DE approach to abemaciclib was associated with significantly fewer treatment interruptions and dose reductions while maintaining similar discontinuation rates compared with SD. These findings suggest that DE may improve early tolerability, support treatment adherence, and optimize clinical outcomes in high-risk HR+, HER2-, EBC patients.