Efficacy and Safety of Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Real-World Studies.

Background: The efficacy and safety of cyclin-dependent kinase (CDK)4/6 inhibitors in patients with breast cancer have been investigated by large-scale trials sponsored by drug companies. A lack of real-world evidence may lead to biases.

Objective: We systematically reviewed the large-scale clinical trials and real-world data to investigate the efficacy and safety of CDK4/6 inhibitors in patients with breast cancer.

Patients And Methods: We searched PubMed, Embase, and Cochrane Library from the inception of each database to January 2024. We included both prospective and retrospective studies reporting the survival outcomes or adverse effects of CDK4/6 inhibitors in patients with breast cancer.

Results: We included 41 prospective trials and 80 retrospective studies involving a total of 69,535 patients. Our meta-analysis of double-arm studies revealed that all types of CDK4/6 inhibitors significantly improved overall survival and progression-free survival. The pooled estimates of the 1-year overall survival (OS) rates and 1-year progression-free survival (PFS) rates in single-arm real-world studies were 74.8% and 49.4% for abemaciclib, 84.1% and 55.7% for palbociclib, and 93.4% and 62.2% for ribobiclib, respectively. In terms of adverse effects, Asian patients were significantly more likely to experience neutropenia and increased alanine aminotransferase, whereas Western patients were significantly more likely to have grade 3 or 4 adverse effects and constipation.

Conclusions: CDK4/6 inhibitors can improve OS and PFS in patients with advanced breast cancer. The incidence of adverse effects may differ with drugs and with ethnicity. On the basis of our findings, clinicians can select suitable CDK4/6 inhibitors for patients by conducting thorough clinical evaluations.