The effect and safety of CDK4/6 inhibitors combined endocrine therapy on HR+, HER2-breast cancer: a meta-analysis of randomized controlled trials.

Introduction: The purpose of this meta-analysis is to evaluate the efficacy and safety of cyclin-dependent kinase4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) on hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC).

Material and methods: A search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases before July 2022.

Results: A total of 19 studies comprising 19,004 patients were eligible for this meta-analysis. This meta-analysis found that for unresectable locally advanced or metastatic HR+, HER2- BC, CDK4/6i combined with ET can significantly improve the progression-free survival (PFS) (hazard ratio = 0.59, p < 0.001), overall survival (OS) (hazard ratio = 0.77, p < 0.001), objective response rate (ORR) [risk ratio (RR) = 1.32, p = 0.001)], disease control rate (DCR) (RR = 1.10, p < 0.001), and clinical benefit response (CBR) (RR = 1.15, p = 0.001). For early HR+, HER2- BC, CDK4/6i combined with ET improved ORR (RR = 1.14, p = 0.05) and invasive disease free survival (iDFS) (hazard ratio = 0.87, p = 0.045) but had no effect on pathologic complete response (pCR) (RR = 1.75, p = 0.33), distant recurrence free survival (DRFS) (hazard ratio = 0.83, p = 0.311), and OS (hazard ratio = 1.08, p = 0.705).

Conclusion: CDK4/6i combined with ET can improve the prognosis of patients with unresectable locally advanced or metastatic HR+, HER2- BC, but it has no obvious effect on patients with early HR+, HER2- BC. It is generally safe and manageable.