A Meta-Analysis Of Cyclin-Dependent Kinase 4/6 Inhibitors In Postmenopausal Patients With Hormone Receptor Positive,HER2-Negative Advanced Breast Cancer

Objective:This meta-analysis was conducted to evaluate the efficacy and safety of cyclin-dependent kinase(CDK)4/6 inhibitors plus endocrine therapy(ET)for postmenopausal hormone receptor positive(HR +),human epidermal growth factor receptor 2-negative(HER2)advanced breast cancer(ABC).Methods:We conducted a systematic search of PubMed,Embase,and Cochrane for a randomized controlled clinical trial of CDK4/6 inhibitors in combination with ET or ET alone in postmenopausal HR-positive,HER2-negative advanced breast cancer.Search is open until December 31,2020.The primary measures we evaluated were progression-free survival(PFS),objective response rate(ORR),clinical benefit rate(CBR),and adverse events(AES).Results:Five controlled trials comparing combination therapy with aromatase inhibitor(AI)and cyclin-dependent kinase(CDK)4/6 inhibitor with AI monotherapy were analyzed,and one controlled trial comparing combination therapy with fluvetilequin 500 mg and C DK4/6 inhibitor with fluvetilequin 500 mg alone.ET combined with CDK4/6 inhibitors significantly improved PFS(hazard ratio: 0.62,95% CI 0.58-0.67),ORR(hazard ratio:0.14,95% CI 0.11-0.18),and CBR(hazard ratio: 0.13,compared with ET monotherapy,95% CI 0.09-0.16).However,endocrine(ET)combined with CDK4/6 inhibitors saw more hematological and gastrointestinal adverse events.The most common grade 3-4 AE is neutropenia.Conclusion:Five controlled trials comparing combination therapy with aromatase inhibitor(AI)and cyclin-dependent kinase(CDK)4/6 inhibitor with AI monotherapy were analyzed,and one controlled trial comparing combination therapy with fluvetilequin 500 mg and C DK4/6 inhibitor with fluvetilequin 500 mg alone.ET combined with CDK4/6 inhibitors significantly improved PFS(hazard ratio: 0.62,95% CI 0.58-0.67),ORR(hazard ratio:0.14,95% CI 0.11-0.18),and CBR(hazard ratio: 0.13,compared with ET monotherapy,95% CI 0.09-0.16).However,endocrine(ET)combined with CDK4/6 inhibitors saw more hematological and gastrointestinal adverse events.The most common grade 3-4 AE is neutropenia.