Association of BMI With Efficacy and Safety of Abemaciclib in Patients With Breast Cancer Treated in the monarchE Trial

Two years of adjuvant abemaciclib plus endocrine therapy (ET) significantly reduced the risk of recurrence and death in patients with hormone receptor-positive, human epidermal growth factor–, node-positive, high-risk breast cancer. Obesity is associated with worse prognosis in early breast cancer. This analysis evaluated efficacy and safety by BMI in monarchE. Groups were defined by baseline BMI as nonoverweight (<25 kg/m 2 ), overweight (25 to < 30 kg/m 2 ), and obesity (≥30 kg/m 2 [subdivided into class 1 [BMI 30 to <35 kg/m 2 ] and class 2 and 3 [BMI ≥35 kg/m 2 ] obesity). Over half (approximately 60%) of the patients enrolled in monarchE had a baseline BMI of ≥25. At a median follow-up of 54 months, abemaciclib + ET showed consistent invasive disease-free survival benefit across baseline BMI groups with hazard ratios (95% CI) of 0.677 (95% CI, 0.551 to 0.831) for nonoverweight, 0.725 (95% CI, 0.580 to 0.907) for overweight, and 0.666 (95% CI, 0.525 to 0.846) for obesity. Across treatment arms, multivariate analysis suggested that class 2 and 3 obesity had a higher risk of recurrence when compared with the nonoverweight group. Similar trends were observed in postbaseline BMI analyses. Similar incidence of grade ≥3 adverse events (AEs) was observed across BMI subgroups. Serious AEs were more common in patients with obesity across treatment arms. Adjuvant abemaciclib + ET showed consistent and clinically meaningful treatment benefit with a comparable safety profile, regardless of BMI. More severe obesity was associated with poorer outcomes, regardless of the treatment.