Impact of body weight and body composition on survival and toxicities in patients receiving CDK4/6 inhibitors for ER+/HER2- metastatic breast cancer.

1087 Background: Body composition influences treatment outcomes and adverse events in many oncologic conditions including metastatic breast cancer (mBC). The objective of our study was to evaluate the impact of body composition measures on progression-free survival (PFS) and adverse events in patients treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors for estrogen receptor-positive (ER+)/HER2- mBC. Methods: A single institution retrospective analysis of 207 patients treated with CDK4/6 inhibitors was conducted. Baseline body weight and body composition measures (total fat, visceral fat, subcutaneous fat, skeletal muscle area, skeletal muscle density and muscular adiposity) were analyzed. PFS was evaluated using Cox proportional hazard models, and logistic regression was used to evaluate the relationship between these variables and adverse events. Early changes in body composition were defined as variations in muscle or fat compartments within 3 months. Low muscle quality was defined as muscle power index value of 1 to 2 Standard Deviations below the normal range. Results: The median age of our cohort was 61 years, with 77% of patients being postmenopausal and 46% identifying themselves as Black. Most patients received palbociclib (76%), followed by abemaciclib (14%) and ribociclib (10%) as part of their treatment. Median BMI was 27.97 kg/m2, with 36% being classified as obese. Sarcopenia was present in 18% of our patients, and 71% had low muscle quality. Higher BMI (HR, 0.96; 95% CI, 0.93-0.99; p 0.01), obesity (HR, 0.60; 95% CI, 0.42-0.86; p = 0.01) and weight (HR, 0.99; 95% CI, 0.98-0.99; p = 0.01) were significantly associated with improved PFS. Modest but statistically significant associations with PFS were observed for total fat (HR 0.99; 95% CI 0.98-0.99; p = 0.01) and subcutaneous fat (HR, 0.99; 95% CI, 0.98-0.99; p = 0.01); however, this was not the case for visceral fat and muscle adiposity. There was no significant association between body muscle compartment distribution (including sarcopenia) and PFS. Early changes in skeletal muscle density were associated with improved PFS (HR, 0.95; 95% CI, 0.91-0.99; p = 0.01), while sarcopenia and low muscle quality were not significant predictors. Grade 3/4 hematologic toxicities were associated with lower muscle area (p = 0.02), but no significant association between fat compartments and adverse events was found. Conclusions: Obesity is associated with improved survival outcomes in patients receiving CKD4/6 inhibitors for ER+/HER2- mBC; furthermore, this effect is driven by subcutaneous fat. Early changes in skeletal density during CDK4/6 inhibitors treatment is a potential predictor of improved outcomes. Muscle area is a potential predictor of treatment toxicities. Our findings suggest that body composition plays an important role in outcomes and adverse events in this group of patients.