Clinical implications of body mass index in metastatic breast cancer patients treated with abemaciclib and endocrine therapy.

BACKGROUND There is limited data regarding the impact of body mass index (BMI) on outcomes in advanced breast cancer (BC), especially in patients treated with endocrine therapy (ET) + CDK 4/6 inhibitors. METHODS Pooled analysis of individual patient-level data from MONARCH 2 and 3 trials. Patients were classified according to baseline BMI into underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2) and divided into two treatment groups: abemaciclib + ET vs. placebo + ET. Primary endpoint was progression-free survival (PFS) according to BMI in each treatment group. Secondary endpoints were response rate (RR), adverse events (AEs) according to BMI, and loss of weight (≥5% from baseline) during treatment. RESULTS This analysis included 1,138 patients (757 received abemaciclib + ET and 381 placebo+ET). There was no difference in PFS between BMI categories in either groups, although normal weight patients presented a numerically higher benefit with abemaciclib + ET (interaction test p=.07). Normal/underweight patients presented higher overall RR in the abemaciclib + ET group compared to overweight/obese (49.4% vs 41.6%, OR = 0.73 95% CI = 0.54 to 0.99), as well as higher neutropenia frequency (51.0% vs 40.4%, p=.004). Weight loss was more frequent in the abemaciclib + ET group (OR = 3.23; 95% CI = 2.09 to5.01). CONCLUSIONS Adding abemaciclib to ET prolongs PFS regardless of BMI, showing that overweight/obese patients also benefit from this regimen. Our results elicit the possibility of a better effect of abemaciclib in normal/underweight patients compared to overweight/obese. More studies analyzing body composition parameters in patients under CDK 4/6 inhibitors may further clarify this hypothesis.