Association between obesity and outcomes of first-line CDK4/6 inhibitor therapy in metastatic breast cancer: a multicenter real-world study

Obesity has been associated with inferior outcomes in early-stage breast cancer, but its clinical relevance in metastatic disease treated with CDK4/6 inhibitors remains uncertain. We retrospectively analyzed 332 patients with hormone receptor-positive/HER2-negative metastatic breast cancer who received first-line ribociclib or palbociclib plus endocrine therapy between 2018 and 2023. Patients were stratified by baseline BMI: <30 kg/m 2 ( n = 221) and ≥ 30 kg/m 2 ( n = 111). Survival outcomes were estimated using Kaplan–Meier and Cox models, and treatment-related adverse events were compared between the groups. The median follow-up duration was 23.1 months. The median PFS was significantly longer in patients with a BMI ≥ 30 kg/m 2 than in those with a BMI < 30 kg/m 2 (46.5 vs. 23.8 months; p = 0.016). In multivariate analysis, BMI ≥ 30 kg/m 2 remained significantly associated with longer PFS (HR, 0.679; 95% CI, 0.468–0.985; p = 0.041). The median OS was not reached in either group. Patients with a BMI ≥ 30 kg/m 2 experienced lower rates of any-grade toxicity and dose-reducing TRAEs. These findings suggest a potential association between BMI and clinical outcomes in this treatment setting. Prospective studies that integrate body composition and pharmacokinetics are required for validation.