Body Mass Index and Outcomes in HR+/HER2- Metastatic Breast Cancer Treated with Palbociclib: Insights from a National...

Background/Objectives: The prognostic and predictive role of BMI in patients with HR+/HER2- MBC remains controversial, particularly in the era of CDK4/6 inhibitors. This study aimed to evaluate the association between baseline BMI and clinical outcomes in patients treated with palbociclib in a real-world setting. Methods: We conducted a multicenter retrospective observational cohort study including 326 patients with HR+/HER2- MBC treated with palbociclib in combination with endocrine therapy across six oncology centers in Romania. Only patients who received palbociclib for at least three months were included. Patients were stratified according to BMI into <25 kg/m² and ≥25 kg/m² groups. PFS and OS were the primary endpoints, while ORR and CBR were secondary endpoints. Results: Among the 326 patients, 66.56% were classified as overweight or obese (BMI ≥ 25 kg/m²). Median PFS was 23.66 months in the BMI < 25 group and 26.78 months in the BMI ≥ 25 group, with no statistically significant difference (HR 0.86; 95% CI 0.62-1.20; p = 0.373). Median OS was not reached in the BMI < 25 group and was 43.73 months in the BMI ≥ 25 group, also without a significant difference (HR 0.82; 95% CI 0.52-1.30; p = 0.397). ORR (29.07% vs. 28.89%) and CBR (90.70% vs. 88.33%) were comparable between BMI groups. In multivariate analysis, liver metastases and brain metastases were independently associated with worse outcomes, whereas BMI was not an independent prognostic factor. Conclusions: In this selected real-world cohort of patients with HR+/HER2- MBC who tolerated at least three months of palbociclib, baseline BMI was not associated with treatment response, PFS, or OS. While clinically informative, these results should not be interpreted as definitive evidence that body weight has no influence on palbociclib efficacy, given the methodological constraints of the analysis. BMI alone may be insufficient to capture the complex interplay between body composition and treatment outcomes, highlighting the need for more refined biomarkers of body composition in this setting.