235P The impact of body mass index (BMI) on the progression-free survival of CDK4/6 inhibitors in metastatic breast cancer patients (MBC)

The main mechanism of CDK4/6 inhibitors is induction of cell-cycle arrest through phosphorylation of the retinoblastoma protein. Metabolic processes such as glucose regulation, adipogenesis and lipid synthesis are affected by cell-cycle regulators. In CDK4/6 trails, patients with high or low body mass index (BMI) were not fully represented. We aimed to investigate the effect of BMI on the progression-free survival (PFS) in HR-positive MBC who received ET plus CDK4/6 inhibitor in second and later line therapy. Patients with metastatic HR-positive breast cancer receiving CDK 4/6 inhibitor (palbociclib or ribociclib) plus ET (letrozole, anastrozole, or fulvestrant) were enrolled in the study from three institutions. 115 patients were retrospectively evaluated between January 2019 and December 2021. The patients were divided into three groups according to BMI level at baseline as follows; normal weight: 18.5-24.9 kg/m2, overweight: 25-29.9 kg/m2 and obese: ≥ 30 kg/m2. Median follow-up was 10.8 months. Comparisons of PFS and BMI categories were performed with Kaplan-Meier curve and log-rank test. The PFS were 9.3 (5.3-13.4) months, 11.1 (9.7-12.6) months, and not reach, in normal weight, obese, and overweight patients, respectively (p=0.02). The overweight patients had a better outcome in term of PFS when palbociclib plus ET and ribociclib plus ET were evaluated separately. The best response of CDK4/6 inhibitors was partial response in all BMI groups (Normal weight:23%, overweight: 43.3%, and obese:32.8%; p=0.06). All toxicities (cardiac, hematological and gastrointestinal) were similar between BMI groups (p>0.05, for all). In this study, we demonstrated that the overweight patients with MBC may benefit more from CDK4/6 inhibitors in term of PFS. Similar toxicity rates were observed in all BMI groups with CDK4/6 inhibitors plus ET.