Efficacy and safety of palbociclib in older women with advanced HR-Positive/HER2-negative breast cancer: a systematic review and meta-analysis

Although cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are already approved for advanced hormone receptor-positive, HER2-negative breast cancer (HR+/HER2– BC), their efficacy and safety in elderly patients remain incompletely defined. We therefore sought to synthesize the evidence on the efficacy and safety of palbociclib (a CDK4/6i) in elderly HR+/HER2– BC patients. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library for studies reporting OS, PFS, and AEs in elderly patients (≥65 years) with HR+/HER2– advanced breast cancer treated with palbociclib. Eligibility criteria included randomized and observational studies with age-specific data. Risk of bias was assessed using Cochrane RoB 2 and ROBINS-I tools. No funding was received. Registration: PROSPERO (CRD42025648485). A p-value of <0.05 denoted statistical significance. We included 3,954 elderly patients treated with palbociclib, of whom 929 (43.2%) had visceral metastases. Palbociclib therapy conferred a significant OS benefit (HR 0.7727; 95% CI 0.6104–0.9780; p = 0.032 and a prolonged PFS (HR 0.6802; 95% CI 0.5452–0.8486; p < 0.001). The most frequent adverse events were neutropenia (RR 5.18; 95% CI 2.65–10.11), decreased white blood cell count (RR 4.80; 95% CI 2.38–9.70), thrombocytopenia (RR 2.57; 95% CI 1.30–5.07), anemia (RR 1.71; 95% CI 1.13–2.58), fatigue (RR 1.06; 95% CI 0.83–1.35), and diarrhea (RR 0.71; 95% CI 0.41–1.24). Palbociclib is associated with significant improvements in both OS and PFS in elderly patients with advanced HR+/HER2– BC. www.crd.york.ac.uk/prospero identifier is CRD42025648485