The CDK4/6 inhibitor in HR-positive advanced breast cancer: A systematic review and meta-analysis

Background:Recently, several high-quality clinical randomized controlled trials (RCTs) have identified that cyclin-dependent kinases (CDKs) 4/6 inhibitors obtained a great safety and efficacy, which can be consequently applied as a combination therapy with letrozole or fulvestrant for women who had advanced breast cancer and progressed while receiving endocrine therapy. In this systemic review, we performed a meta-analysis to explore whether CDK4/6 inhibitors had a significantly benefit to treating hormone receptor-positive (HR-positive)/human epidermal growth factor receptor 2 negative (HER2-negative) advanced breast cancer.Methods:The data for meta-analysis were collected from MEDLINE, EMBASE, and Cochrane Library from January 1980 to December 2017, and eventually 3182 patients from 6 RCTs were included.Results:The result showed the CDK4/6 inhibitor group had a longer progression-free survival (PFS) (hazard ratio=0.51; 95% confidence interval [CI], 0.46-0.57, P < .00001), a better objective response (risk rate=1.53; 95% CI, 1.35-1.74, P < .00001), as well as a better clinical benefit response (risk rate=1.29; 95% CI, 1.13-1.47, P=.0001). Besides, subgroup analyses of PFS according to stratification factors and other baseline characteristics confirmed a great performance of CDK4/6 inhibitors across the all subgroups. And sensitive analysis showed that all outcomes were stable except Finn 2014 trail.Conclusion:CDK4/6 inhibitors can significantly prolong the PFS and improve the objective response and clinical benefit response among the patients with HR-positive/ HER2-negative advanced breast cancer.