Background
Two years of adjuvant abemaciclib plus endocrine therapy (ET) demonstrated statistically significant and clinically meaningful improvement over ET alone in invasive disease-free survival (iDFS) and distant relapse-free survival (DRFS) in patients with hormone receptor–positive/HER2-negative (HR+/HER2–), node-positive, high-risk early breast cancer. The primary overall survival (OS [secondary end point)]) and updated iDFS and DRFS are reported here.
Methods
monarchE is an open-label, randomized, phase 3 trial in patients with HR+/HER2–, high-risk early breast cancer. Patients were randomized 1:1 to receive ET for at least 5 years with or without abemaciclib for the first 2 years. High-risk early breast cancer was defined as either 4 or more positive axillary lymph nodes (ALN), or 1 to 3 ALN plus either grade 3 disease and/or tumor 5 cm or more (cohort 1). Patients with 1 to 3 positive ALN and central Ki67 ≥ 20% were enrolled to cohort 2. The intent-to-treat (ITT) population consisted of cohorts 1 (n = 5120) and 2 (n =517). Hazard ratios (HR) for efficacy end points were estimated using the Cox proportional hazard model. The primary OS analysis was triggered by approximately 650 deaths in the ITT population to allow adequate follow-up time.
Results
In the ITT population (median follow-up: 6.3 years), 301 patients in the abemaciclib plus ET and 360 patients in the ET arm had died. The addition of abemaciclib to ET reduced the risk of death by 15.8% vs ET (HR, 0.84; 95% CI, 0.72-0.98; P = .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 plus ET vs 70.9% with ET, and DRFS was 80.0% vs 74.9% (absolute benefit: 6.5% and 5.1%, respectively). More patients in the ET arm (52%) received subsequent CDK4/6 inhibitors in any line metastatic setting than in the abemaciclib plus ET arm (34%). In cohort 1, iDFS, DRFS, and OS were consistent with the ITT population. Long-term safety data did not support concerns of delayed toxicities.
Conclusions
The addition of 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 early breast cancer. At 7 years, abemaciclib plus ET demonstrated a sustained iDFS and DRFS benefit.
Previously presented at ESMO 2025.
Study is sponsored by Eli Lilly and Company.
