Aims: An updated efficacy analysis for node positive subgroups in monarchE Cohort 1 (C1) is presented.
Methods: monarchE is a phase 3 trial in high-risk HR+, HER2- EBC. Patients were randomized 1:1 to ET for ≥5 years +/- abemaciclib for 2 years. High-risk EBC was defined as either 1-3 ALN (N1) with grade-3 disease and/or tumor≥5 cm or, ≥4 ALN (N2: 4-9, N3: ≥10) (C1). A smaller group of patients (C2) were enrolled with N1, Grade ≤2, tumor size <5 cm, and central Ki-67 ≥20%. IDFS/DRFS/OS were assessed in C1 nodal subgroups.
Results: In C1 (N=5120), 1761 (34.4%) patients had N1, 2223 (43.4%) had N2, and 1123 (21.9%) had N3 disease. With median follow-up of 76.8 months in C1, in the ET arm, a comparable number of patients with N1 and N2 disease had IDFS events at 6-years (21.6%/25.4%), while event number was higher in N3 (38.1%). A similar trend was observed in DRFS/OS. Adding abemaciclib to ET reduced the risk of developing an IDFS event vs ET alone across subgroups: N1 HR=0.75 [0.61,0.94], N2 HR=0.69 [0.57,0.82] and N3 HR=0.73 [0.59,0.89]. Risk of developing DRFS events was reduced vs ET alone: N1 HR=0.75 [0.59,0.95], N2 HR=0.69 [0.57,0.84], and N3 HR=0.74 [0.60,0.92]. Abemaciclib+ET consistently reduced the risk of death vs ET alone across ALN subgroups: N1 HR=0.88 [0.65,1.18], N2 HR=0.85 [0.66,1.09], and N3 HR=0.73 [0.56,0.96].
Conclusions: In the ET arm, patients with N1 ≥1 additional risk factor had recurrence and death risks comparable to patients with N2, while patients with N3 had poorer prognosis. Addition of adjuvant abemaciclib + 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 EBC.