Two years of adjuvant abemaciclib+endocrine therapy (ET) resulted in sustained improvement in IDFS (HR=0.68,5-year rates:84%vs76% abemaciclib+ET vs ET, 8% absolute benefit) in patients with HR+, HER2-, node-positive, high-risk early BC (EBC) in monarchE. Obesity is an established factor influencing the biology and prognosis of BC. Here we report efficacy/safety by BMI in patients in monarchE.
Patients were randomised 1:1 to receive endocrine therapy (ET) for ≥5 years +/- abemaciclib for 2 years. Groups were defined by baseline BMI (kg/m2): obese (≥30)/overweight (25<30)/non-overweight (<25). IDFS/DRFS in each group was assessed using Kaplan-Meier method and unstratified Cox model.
1507 patients (27%) were obese, 1762 (32%) were overweight, and 2227 (41%) were non-overweight. Most obese patients were postmenopausal (67%), received AI as first ET (75%) and a substantial proportion (47%) had ≥4 comorbidities, vs 60%/69%/34% among overweight patients and 47%/63%/30% among non-overweight, respectively. Patients ≥65 years constituted 18%/17%/12% of these groups. A consistent treatment benefit in IDFS was observed in abemaciclib+ET across all BMI groups: obese (HR=0.67[95%CI:0.53,0.85]), overweight (HR=0.73,95%CI:0.58,0.91), and non-overweight (HR=0.68[95%CI:0.55,0.83]), interaction p-value=0.858. 5-year IDFS rates in the ET arm were lowest in obese patients (74%) and similar for overweight/non-overweight patients (77% in each). With abemaciclib+ET, absolute improvements in IDFS were 8.8%/5.8%/7.9% across each respective BMI group. Similar findings were observed for DRFS. Obese patients had fewer grade≥3 (G≥3) neutropenia (14%vs19%vs24%). Despite higher G≥3 diarrhea in obese patients (10%vs8%vs6%), related dose reductions (18%vs18%vs17%) and discontinuations (5%vs6%vs5%) were similar in all 3 groups. Abemaciclib dose reductions related to AEs were 41%vs43%vs45% in obese/overweight/non-overweight groups, respectively. G≥3 ALT elevations were low in all groups (2%vs3%vs3%). Serious AEs (SAEs) were more common in obese patients, across treatment arms (abemaciclib+ET:20%vs16%vs13%;ET: 11%vs8%vs9%) (fatal SAEs-abemaciclib+ET:3%vs2%vs1%; ET:2%vs1%vs1%).
In patients with high-risk EBC, adjuvant abemaciclib+ET showed consistent and clinically meaningful treatment benefit across BMI subgroups, plus a manageable safety profile.