Safety and Efficacy of Palbociclib and Endocrine Therapy Versus Endocrine Therapy Alone in HR+/HER 2- Breast Cancer Patients; a Systematic Review and Meta-Analysis.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as novel agents in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. Palbociclib, when used in combination with endocrine therapy (ET), has shown promising results in this domain; however, conclusive evidence is still inadequate. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, comparing palbociclib plus ET with ET alone in HR+/HER2- advanced breast cancer patients. A total of 15 studies comprising 13,827 patients were included. Palbociclib plus ET significantly improved overall survival (HR=0.83, 95% CI: 0.76-0.91; P<0.0001) and progression-free survival (HR=0.60, 95% CI: 0.54-0.67; P<0.0001) compared with ET alone. Significant differences were also observed in objective response rate (OR=1.85, 95% CI: 1.45-2.35; P<0.0001), partial response (OR=1.89, 95% CI: 1.43-2.48; P<0.0001), disease control rate (OR=2.42, 95% CI: 1.77-3.29; P<0.0001), and progressive disease (OR=0.37, 95% CI: 0.21-0.64; P=0.0005). No significant differences were observed for complete response or stable disease. In addition, palbociclib plus ET was associated with significantly increased adverse events, including neutropenia, leukopenia, thrombocytopenia, anemia, and febrile neutropenia. Palbociclib plus ET exhibits supremacy over ET alone in terms of survival and disease-control outcomes in HR+/HER2- advanced or metastatic breast cancer. However, there exists a significant trade-off in terms of increased adverse events, especially hematological toxicity, in the palbociclib plus ET group as compared with the ET group.