Abstract PS1-11-06: Impact of sarcopenia on efficacy and toxicity profile of CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer patients: a real-world analysis

Abstract Background: CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are standard first-line treatment in HR+/HER2- metastatic breast cancer (mBC). Sarcopenia is prevalent in cancer patients and linked to poorer outcomes and higher toxicity, but its role in CDK4/6i-treated patients remains under-investigated. This real-world retrospective study evaluates sarcopenia's impact on survival outcomes (PFS/OS) and toxicity in mBC patients receiving CDK4/6i. Methods: Retrospective analysis of clinical and radiological data from patients (pts) with histologically confirmed HR+/HER2- stage IV mBC at Sant'Andrea University Hospital was performed. All pts had de novo metastatic or relapsed disease treated with first-line CDK4/6i plus ET. Sarcopenia was assessed using baseline CT scans with third lumbar vertebra (L3) as reference. Body composition analysis used AI-based automatic segmentation software (DeepCatch). Skeletal muscle index (SMI) cutoff 0.05). Multivariate analysis confirmed BMI as continuous variable (p=0.01) and severe toxicity grading (p=0.046, OR=3.118) as independent sarcopenia predictors. Conclusions: In mBC patients treated with first-line CDK4/6i plus ET, BMI and high-grade toxicity emerged as independent sarcopenia predictors. However, sarcopenia did not represent a negative prognostic factor for PFS and OS in our analysis. The significant correlation between sarcopenia and severe toxicity suggests need for nutritional screening and closer monitoring of sarcopenic patients to optimize treatment tolerability. These findings support implementing body composition assessment in clinical practice for patients receiving CDK4/6i plus ET. Further investigation is warranted to validate and expand these results. Citation Format: D. Drittone, M. Zerunian, M. Mariniello, C. Lucci, L. Esposito, N. Spiezia, M. Delle Chiaie, F. Schipilliti, G. Arrivi, M. Francone, F. Mazzuca, S. Pisegna. Impact of sarcopenia on efficacy and toxicity profile of CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer patients: a real-world analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-11-06.