CDK4/6 Inhibitors in Combination With Hormone Therapy for HR+/HER2- Advanced Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials

We conducted a meta-analysis that aimed to assess the efficacy and toxicity of cyclin-dependent kinase (CDK) 4/6 inhibitors in hormone receptor-positive (HRD)/human epidermal growth factor receptor 2-negative (HER2(-)) advanced breast cancer (ABC) that assessed 7 randomized clinical trials involving 3854 patients. CDK4/6 inhibitors can significantly prolong the progression-free survival of patients with HR+/HER2(-) ABC. The combined regimen of CDK4/6 inhibitors and hormone therapy results in a higher risk of adverse events. Background: This meta-analysis of randomized controlled trials aimed to comprehensively assess the efficacy and toxicity of cyclin-dependent kinase (CDK) 4/6 inhibitors in advanced breast cancer (ABC) with hormone-receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2(-)) disease. Methods: We performed a systematical search using Cochrane Library, PubMed, Embase, and Web of Science up to March 2018. Only phase 2 and 3 randomized clinical trials assessing the efficacy and toxicity of the combination regimen of CDK4/6 inhibitors plus hormone therapy compared with hormone therapy alone were eligible for this meta-analysis. The pooled analyses of relative risk (RR) and hazard ratio were carried out by Stata software. Results: A total of 7 randomized controlled trials including 3854 patients with HR+/HER2(-) ABC were included in this meta-analysis. The pooled hazard ratio for progression-free survival was 0.54 (95% confidence interval, 0.49-0.59; P < .001), and the pooled RR for the objective response rate in all intent-to-treat patients was 1.51 (95% confidence interval, 1.26-1.81; P < .001). The pooled RRs for all grade adverse events (AEs) and grade 3/4 AEs were 1.07 (95% confidence interval, 1.03-1.11; P < .001) and 2.81 (95% confidence interval, 2.54-3.11; P < .001), respectively. However, to investigate the influence of CDK4/6 inhibitors on overall survival, sufficient follow-up is still needed. Conclusion: CDK4/6 inhibitors plus hormone therapy can significantly prolong the progression-free survival of patients with HR+/HER2(-) ABC and improve the objective response rate compared to conventional hormone therapy alone. The combined regimen results in a higher risk of AEs, especially grade 3/4 AEs. (C) 2018 Elsevier Inc. All rights reserved.