Adjuvant Abemaciclib Combined With Endocrine Therapy for High-Risk Early Breast Cancer: Updated Efficacy and Ki-67 Analysis From the monarchE Study.

Background Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in HR+, HER2-, node-positive, high risk early breast cancer (EBC) at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome (PO) analysis and an additional follow-up analysis (AFU1). Patients and methods This global, phase 3, open-label trial, randomized (1:1) 5637 patients to adjuvant ET for ≥5 years +/- abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALN), or 1-3 positive ALN and either Grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALN and centrally determined high Ki-67 index (≥20%). Primary endpoint was IDFS in the intent-to-treat population (Cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. Results At the PO analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event (HR=0.71, 95% CI: 0.58, 0.87; nominal p=0.0009). At the AFU1 analysis, with 27 months median follow-up and 90% of patients off-treatment, IDFS (HR=0.70, 95% CI=0.59, 0.82; nominal p Conclusion Abemaciclib+ET significantly improved IDFS in patients with HR+, HER-, node-positive, high risk EBC, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.