Cancer Center, Sichuan University, Chengdu, China.
Department of Thoracic Surgery, Sichuan University, Chengdu, China.
Clin Breast Cancer. 2018 Oct;18(5):e943-e953. doi: 10.1016/j.clbc.2018.04.017. Epub 2018 May 4.
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.
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.
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.
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.
本荟萃分析纳入了随机对照试验，旨在全面评估细胞周期蛋白依赖性激酶（CDK）4/6 抑制剂在激素受体阳性（HR）和人表皮生长因子受体 2 阴性（HER2）的晚期乳腺癌（ABC）中的疗效和毒性。
我们系统地检索了 Cochrane 图书馆、PubMed、Embase 和 Web of Science，检索时间截至 2018 年 3 月。仅纳入评估 CDK4/6 抑制剂联合激素治疗与单独激素治疗相比在疗效和毒性方面的 2 期和 3 期随机临床试验。采用 Stata 软件进行相对风险（RR）和风险比的汇总分析。
共有 7 项随机对照试验（共纳入 3854 例 HR/HER2 ABC 患者）纳入本荟萃分析。无进展生存的汇总风险比为 0.54（95%置信区间，0.49-0.59；P<0.001），所有意向治疗患者的客观缓解率的汇总 RR 为 1.51（95%置信区间，1.26-1.81；P<0.001）。所有级别不良事件（AE）和 3/4 级 AE 的汇总 RR 分别为 1.07（95%置信区间，1.03-1.11；P<0.001）和 2.81（95%置信区间，2.54-3.11；P<0.001）。然而，要评估 CDK4/6 抑制剂对总生存的影响，还需要足够的随访。
与单独使用常规激素治疗相比，CDK4/6 抑制剂联合激素治疗能显著延长 HR/HER2 ABC 患者的无进展生存期，并提高客观缓解率。联合方案导致 AE 发生率增加，特别是 3/4 级 AE。
