Survival Benefits of Palbociclib Plus Endocrine Therapy in HR+/HER2- Advanced Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Trials

Abstract

Context: Endocrine therapy remains the standard of care for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (BC), but its efficacy is limited in patients with prior endocrine exposure. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), such as palbociclib, have emerged as a promising strategy to enhance treatment outcomes. Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy of palbociclib combined with endocrine therapy (ET) versus endocrine therapy alone in improving survival outcomes. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science up to November 9, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) comparing palbociclib plus ET with ET alone or placebo plus ET in HR+/HER2– advanced or metastatic BC patients were included. Outcomes assessed were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled. Results: Seven RCTs, including 1,758 patients, met inclusion criteria. Pooled analysis demonstrated that palbociclib combined with ET significantly improved PFS compared with ET alone (HR = 0.492; P < 0.001). A trend toward improved OS was observed (HR = 0.883; P = 0.075), though this did not reach statistical significance. Subgroup analyses and bias assessments confirmed consistent efficacy across populations and low risk of methodological bias, with no evidence of publication bias. Conclusions: Palbociclib combined with ET provides substantial improvements in PFS and demonstrates a favorable trend in OS for patients with HR+/HER2– advanced BC.