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).

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.

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<0.0001) and DRFS (HR=0.69, 95% CI=0.57, 0.83; nominal p<0.0001) benefit was maintained. The absolute improvement in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. While Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data was consistent with the known abemaciclib risk profile.

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.