Efficacy And Safety Of CDK4/6 Inhibitors Combined With Endocrine Therapy In Advanced Breast Cancer: A Meta-analysis

Objective: To systematically review the efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer.Methods: Pub Med,EMBase,The Cochrane Library,CNKI,Wan Fang Data and VIP databases were electronically searched to collect randomized controlled trials(RCTs)of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer from inception to Oct 13 th,2017.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies,then,meta-analysis was performed by using Rev Man 5.3 software.Results: A total of 4 RCTs involving 2 524 patients were included.The results of metaanalysis showed that: compared with placebo combined with endocrine therapy,CDK4/6 inhibitors combined with endocrine therapy could prolong the median progression free survival(RR=0.53,95%CI 0.47 to 0.60,P<0.000 01)and improve the objective response rate(RR=1.67,95%CI 1.47 to 1.91,P<0.000 01),and the differences were statistically significant.While there was no statistical difference in clinical benefit rate(RR=0.59,95%CI 0.75 to 1.19,P=0.64).In terms of adverse reactions,CDK4/6 inhibitors combined with endocrine therapy had higher rates of neutropenia(RR=49.76,95%CI 26.85 to 90.21,P<0.000 01),leukopenia(RR=48.69,95%CI 18.74 to 133.61,P<0.000 01),fatigue(RR=3.11,95%CI1.37 to 7.08,P=0.007)and anemia(RR=2.96,95%CI 1.61 to 5.42,P=0.000 3).There was no significantly difference between two groups in nausea,diarrhea,and decreased appetite.Conclusion: CDK4/6 inhibitors combined with endocrine therapy for the patients with advanced breast cancer can improve median progression free survival and objective response rate,while increasing the incidence of adverse events such as neutropenia,leukopenia,fatigue and anemia.