The Combination of CDK 4/6 Inhibitors plus Endocrine Treatment versus Endocrine Treatment Alone in Hormone-receptor (HR)-Positive breast Cancer: a Systematic Review and Meta-analysis.

Background: The identification of the novel targeted therapy i.e., cyclin-dependent kinases (CDKs) 4/6 inhibitor as combined with the endocrine regimen revealed a considerable capability to increase the managements' effectivity of hormone-receptor-positive (HR+) and HER2- breast cancer (BC). Objective: This study aims to compare the latter combination strategies versus hormonal therapy alone to determine its applicability in the treatment of HR+/HER2- BC. Methods: We established the review based on the clinical trials as collected from several scientific databases from January 2011 to April 2021. RevMan 5.4 was utilized in statistical analysis and risk of bias (RoB) measurement. 5110 participants from 9 different trials were included in this review with similar baseline characteristics. Results: According to our analysis of the intention-to-treat (ITT) group, CDK 4/6 inhibitor arms exhibited better overall response rate (ORR) as indicated by the relative risk (RR) (randomized-effect model (REM), 1.59 [1.37, 1.86]; 95% confidence interval (CI); P <0.00001) and higher clinical benefit rate (CBR) (RR, 1.22 [1.13, 1.32]; 95% CI; REM; P <0.00001). The combination regiment also proved to be effective in reducing the rate of progressive disease (PD) in the ITT group (RR 0.46 [0.39, 0.54]; CI 95%; FEM; P <0.00001. Although the rate of adverse effects especially the hematological reactions was significantly lower in the endocrine alone arm, other system reactions were fairly comparable. Conclusion: The introduction of CDK 4/6 inhibitor to the endocrine-based regiment is proved beneficial to patients with HR+/HER2- BC even though the most recommended anti-hormonal to be combined remains questionable.