Aims: An updated efficacy analysis (76.8 months median follow-up; data cutoff 15 July 2025) for key subgroups in Cohort 1 (C1) of monarchE is presented.
Methods: Patients were randomized (1:1) to receive ET for at least 5-years ± abemaciclib for the first 2-years. High-risk early breast cancer (EBC) was defined as 1-3 axillary lymph nodes (ALN) with grade 3 disease and/or tumor ≥5 cm, or ≥4 positive ALN (Cohort 1). For subgroups: age (≤40/>40 years), menopausal status (pre/post), prior chemotherapy (neo-adjuvant (NAC)/adjuvant (Adj)), region (North America/Europe, Asia, other), treatment effect was estimated using unstratified Cox PH model within each subgroup with interaction effects between treatment arms and subgroup. Landmark analysis within each subgroup was performed using Kaplan Meier (KM) method.
Results: Invasive Disease Free survival (IDFS) benefit was consistent across subgroups: age ≤40 HR=0.661 (95%CI:0.496-0.880, 6-year Δ8.3%); >40 HR=0.743 (95%CI:0.656-0.842, 6-year Δ5.7%); premenopausal HR=0.681 (95%CI:0.566-0.819, 6-year Δ7.2%), postmenopausal HR=0.764 (95%CI:0.660-0.885, 6-year Δ5.2%); NAC HR=0.690 (95%CI:0.584-0.815, 6-year Δ9.9%), Adj HR=0.751 (95%CI; (0.636, 0.886 6-year Δ3.9%); North America/Europe HR=0.731 (95%CI:0.622-0.860, 6-year Δ5.5%), Asia HR=0.762 (95%CI:0.583-0.995, 6-year Δ5.7%), other HR=0.707 (95%CI:0.575-0.869, 6-year Δ7.4%). Recurrence risk was higher in ET only arm, for patients ≤40-years vs >40-years (6-year IDFS rates: 69% vs 74%) and in neoadjuvant chemotherapy vs adjuvant (63% vs 80%). DRFS and overall survival benefit were consistent across all subgroups.
Conclusions: In patients with high-risk EBC, abemaciclib+ET showed consistent and clinically meaningful, long-term treatment benefit across key subgroups. Patients who were younger or received neoadjuvant chemotherapy previously shown to have high risk features, had poorer prognosis among subgroups. These data support adjuvant abemaciclib use in eligible patients to reduce recurrence and mortality risk.