Impact of body mass index (BMI) on efficacy and safety of abemaciclib in breast cancer patients (pts) treated in the monarchE trial.

520 Background: Two years (yrs) of adjuvant abemaciclib + endocrine therapy (ET) resulted in sustained improvement in invasive disease-free survival (IDFS HR=0.68, 5 yrs rates: 84% abemaciclib + ET vs 76% ET, 8% absolute benefit) in pts with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, high-risk early breast cancer (EBC). Obesity is an established factor influencing the biology and prognosis of breast cancer; however, the specific impact on treatment (tx) outcomes remains uncertain. Here we report efficacy and safety by BMI in monarchE. Methods: Pts were randomized 1:1 to receive ET for at least 5 yrs +/- abemaciclib for 2 yrs. Groups were defined by baseline BMI (kg/m 2 ): as obese (≥30), overweight (25<30), and non-overweight (<25). IDFS/DRFS in each group was assessed using Kaplan-Meier method and unstratified Cox model. Safety was summarized by subgroup. Results: 1507 pts (27%) were obese, 1762 (32%) were overweight, and 2227 (41%) were non-overweight. Most obese pts were postmenopausal (67%), received aromatase inhibitor as first ET (75%) and a substantial proportion (47%) had ≥4 comorbidities, vs 60%, 69%, 34% among overweight pts and 47%, 63%, 30% among non-overweight, respectively. Pts ≥65 yrs constituted 18%, 17% and 12% of these groups. Disease characteristics were balanced across BMI groups. A consistent tx benefit in IDFS was observed with the addition of abemaciclib to ET across all 3 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), with an interaction p-value of 0.858. 5yr IDFS rates in the ET arm were lowest in obese pts (74%) and similar for overweight and non-overweight pts (77% in each). In the abemaciclib + ET arm, absolute improvements in IDFS were 8.8%, 5.8% and 7.9% across each respective BMI group. Similar findings were observed for DRFS. Obese pts had fewer grade≥3 (G≥3) neutropenia, and related dose hold/reductions. Despite higher G≥3 diarrhea in obese pts, related dose reductions and discontinuations were similar in all 3 groups. G≥3 ALT elevations were low in all groups. Serious AEs (SAEs) were more common in obese pts, across tx arms (Table). Conclusions: In pts with high-risk EBC, adjuvant abemaciclib + ET showed consistent and clinically meaningful tx benefit across BMI subgroups, along with a manageable safety profile. Additional analyses are planned to adjust for the impact of confounding factors such as comorbidities. Clinical trial information: NCT03155997 . Abemaciclib + ET ET % Obese n=723 Overweight n=886 Non-overweight n=1118 Obese n=784 Overweight n=876 Non-overweight n=1109 ≥1AE Any grade 98 99 98 91 89 88 G ≥3 50 48 52 21 15 15 Neutropenia 14 19 24 0.1 0.5 2 Diarrhea 10 8 6 0.3 0.2 0.2 ALT 2 3 3 1 0.7 0.5 All tx discontinuation due to AE 7 6 5 2 0.3 0.5 Dose reductionsrelated to anyAE/diarrhea/neutropenia 41/18/6 43/18/6 45/17/11 - - - ≥1 SAE Fatal 203 162 131 112 81 91