Aims: We report primary OS (secondary endpoint) and updated IDFS and DRFS from the monarchE trial.
Methods: monarchE is an open-label, phase 3 trial in patients with HR+, HER2-, high-risk EBC. Patients were randomized 1:1 to ET for ≥5 years ± abemaciclib for the first 2 years. High-risk EBC was defined as either ≥4 positive axillary lymph nodes (ALN), or 1-3 ALN + either Grade 3 disease and/or tumor ≥5 cm (Cohort 1). Cohort 2 enrolled patients with 1-3+ ALN and central Ki67 ≥20%. The intent-to-treat (ITT) population consisted of Cohorts 1 (n=5120) and 2 (n=517). Primary OS analysis was triggered by approx. 650 deaths in ITT population.
Results: In the ITT population (median follow-up: 6.3 years) 301 patients in the abemaciclib+ET and 360 patients in the ET arm had died. Adding abemaciclib to ET reduced the risk of death by 15.8% vs ET (HR=0.84;95%CI:0.72–0.98; P=0.027), meeting the prespecified boundary for significance. OS benefit was consistent across prespecified subgroups. IDFS and DRFS benefit persisted up to 7-years (HR=0.73;95%CI:0.66-0.82 and 0.75;0.66-0.84, respectively). At 7-years, IDFS was 77.4% with abemaciclib+ET vs 70.9% with ET, and DRFS was 80.0% vs 74.9% (absolute benefit:6.5% and 5.1%, respectively). In Cohort 1, IDFS/DRFS/OS were consistent with the ITT population. Long-term safety data did not support concerns of delayed toxicities.
Conclusions: Adding 2-years of adjuvant abemaciclib to ET resulted in statistically significant and clinically meaningful improvement in OS over ET in patients with HR+, HER2−, node-positive, high-risk EBC. At 7-years, abemaciclib+ET demonstrated a sustained IDFS and DRFS benefit.