Background
Adding 2 years of adjuvant abemaciclib to endocrine therapy (ET) improved overall survival (OS) in patients with hormone receptor–positive/HER2-negative (HR+/HER2–), node-positive, high-risk early breast cancer. At 7 years, abemaciclib plus ET demonstrated sustained invasive disease-free survival (iDFS; HR, 0.73; 95% CI, 0.66-0.82) ) and distant relapse-free survival (DRFS; HR, 0.75; 95% CI, 0.66-0.84) benefits. Previous monarchE data highlight that patients with N1 disease (1-3 axillary lymph nodes [ALN]) and additional risk factors (grade 3 and/or large tumor size) are at high recurrence risk. Here we present subgroup analyses by ALN (N1, N2, N3).
Methods
In the monarchE open-label, phase 3 trial, patients were randomized 1:1 to ET for 5 years or more with or without abemaciclib for 2 years (treatment period). High-risk early breast cancer was defined as either 1 to 3 ALN (N1) with grade 3 disease and/or tumor 5 cm or more, or 4 ALN or more (N2: 4-9, N3: ≥ 10) (cohort 1). Patients in cohort 2 had N1 disease with grade 2 or less, tumor size less than 5 cm and Ki-67 > 20%. iDFS, DRFS, and overall survival (OS) were assessed in cohort 1.
Results
Of 5120 randomized patients in cohort 1, 1761 (34.4%) had N1, 2223 (43.4%) had N2, and 1123 (21.9%) had N3 disease. Patients with N1 high-risk disease presented more grade 3 tumors (69%) and Ki67 ≥ 20% (49%) vs N2 (27% and 33%) and N3 (28% and 36%). At a median follow-up time of 76.8 months in cohort 1, in the ET arm, a comparable number of patients with N1 and N2 disease had iDFS events at 6 years (21.6% and 25.4%), with notably higher rate (38.1%) in the N3 group. A similar trend was observed in DRFS and OS. Adding abemaciclib to ET reduced the risk of developing an iDFS event across subgroups: N1 (HR, 0.75; 95% CI, 0.61-0.94), N2 (HR, 0.69; 95% CI, 0.57-0.82), and N3 (HR, 0.73; 95% CI, 0.59,0.89) vs ET. The risk of developing DRFS events was reduced: N1 (HR, 0.75; 95% CI, 0.59-0.95), N2 (HR, 0.69; 95% CI, 0.57-0.84), and N3 (HR, 0.74; 95% CI 0.60-0.92). Abemaciclib plus ET consistently reduced the risk of death vs ET across ALN subgroups: N1 (HR, 0.88; 95% CI, 0.65-1.18), N2 (HR, 0.85; 95% CI, 0.66-1.09), and N3 (HR, 0.73; 95% CI, 0.56,0.96).
Conclusions
In the ET arm, patients with N1 plus one or more additional risk factor had recurrence and death risks comparable to patients with N2, while patients with N3 had poorer prognosis. Adjuvant abemaciclib plus ET led to a clinically meaningful reduction in the risk of recurrence and death regardless of nodal burden, confirming the consistent and sustained benefit of 2 years of treatment with abemaciclib and supporting its use in eligible patients with node-positive, high-risk early breast cancer.
Previously presented at SABCS 2025.
Study is sponsored by Eli Lilly and Company.
