Safety of Abemaciclib in Indian Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced and/or Metastatic Breast Cancer: A Multicenter, Nonrandomized, Open-Label, Single-Arm, Phase 4 Study.

Background: Global phase III trials demonstrated efficacy of abemaciclib in patients with HR +/HER2- metastatic breast cancer (BC) as a first-line therapy in combination with a nonsteroidal aromatase inhibitor (MONARCH-3) or with fulvestrant following progression after endocrine therapy (ET) (MONARCH-2). However, there is limited data on safety and tolerability of abemaciclib plus ET in the metastatic BC setting among Indian patients, which the present study aims to address. Materials and Methods: An open-label, single-arm, phase IV study was conducted across 16 centers in India to assess the safety and tolerability of abemaciclib in patients with HR +/HER2- locally advanced or metastatic BC. Patients were assigned to either cohort A, ET-naive patients (abemaciclib + anastrozole/letrozole) or cohort B, patients progressing after previous ET (abemaciclib + fulvestrant), targeting the same patient population as the global phase III MONARCH-3 and MONARCH-2 trials, respectively. Primary endpoints were all-cause adverse events (AEs) including serious AEs (SAEs). Statistical Analysis: The statistical analysis was conducted using SAS Version 9.4. Results: Two hundred patients were enrolled, with a mean age of 54 years, most (77.0%) were aged ≤ 65 years. The median duration of exposure was similar in both cohorts (cohort A vs. B: 24.3 vs. 24.4 weeks). Overall, 75.5 % of patients reported all-cause AEs, of which 38.5% of the patients reported AEs Common Terminology Criteria for Adverse Events grade 3 and above. The most common grade 3 and above all-cause AEs for abemaciclib were neutropenia (19.0%), followed by anemia (14.0%) and diarrhea (5.5%). Fourteen (7.0%) patients encountered SAEs, including infections (2.0%) and gastrointestinal disorders (1.5%). Most of the patients continued their treatments with appropriate dose reductions (25.5%) and dose omissions (40.5%), and only 2.5% of patients discontinued study treatment due to treatment-related AEs. Conclusion: Abemaciclib in combination with ET was found to have an acceptable tolerability in Indian patients with HR +/HER2- advanced and metastatic BC, consistent with the established safety data as reported in the pivotal global studies. No new clinical safety concerns were identified, with most of the reported AEs and SAEs managed by dose adjustments.