Department of Internal Medicine-Oncology, The First Hospital of Lanzhou University, Lanzhou, China.
Thorac Cancer. 2019 Apr;10(4):607-623. doi: 10.1111/1759-7714.12971. Epub 2019 Feb 7.
Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, and most clinically curable patients are diagnosed with locally advanced disease. Although the efficacy of standard platinum-based chemotherapy doublets is relatively limited. The effect of immune checkpoint inhibitors (ICIs) remains controversial, and its role in the first-line treatment of advanced NSCLC is obscure. Thus, we carried out a systematic review and meta-analysis to compare the efficacy and safety of ICIs for advanced NSCLC.
The PubMed, Cochrane Central Register Trial, and American Society of Clinical Oncology databases were searched from inception to 30 April 2018. We searched for randomized controlled trials comparing single-agent programmed cell death protein 1/programmed death-ligand 1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) or cytotoxic T-lymphocyte-associated antigen 4 inhibitor (ipilimumab) with chemotherapy in NSCLC patients. Progression-free survival, overall survival, objective response rate, and adverse events were pooled for meta-analysis by Review Manager (RevMan version 5.3) software.
After exclusion of ineligible studies, 12 eligible randomized controlled trials were included. Data showed that ICIs significantly improved progression-free survival (HR 0.66, 95% CI 0.57-0.77, P < 0.00001), overall survival (HR 0.77, 95% CI 0.64-0.91, P = 0.003), and but not objective response rate (RR 1.97, 95% CI 1.25-3.13, P = 0.004) in all unselected NSCLC populations. However, they failed to increase the OS of programmed death-ligand 1 = 1-49% subgroup (HR 0.78, 95% CI 0.51-1.19, P = 0.25) and PFS of programmed death-ligand 1<1% subgroup (HR 0.85; 95%CI 0.70 to 1.03, P=0.09) in ICIs+chemotherapy over chemotherapy. Meanwhile, OS of programmed death-ligand =1-49% subgroup (HR 0.92; 95%CI 0.77 to 1.10, P=0.36) and PFS of programmed death-ligand 1≥50% subgroup (HR 0.76; 95%CI 0.52 to 1.11, P=0.15) showed no significant differences in ICIs over chemotherapy. Furthermore, fewer adverse events were observed in the ICIs groups than control groups.
ICIs are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for ICIs.
非小细胞肺癌（NSCLC）是肺癌的主要类型，大多数可临床治愈的患者被诊断为局部晚期疾病。虽然标准铂类化疗双联方案的疗效相对有限，但免疫检查点抑制剂（ICIs）的疗效仍存在争议，其在晚期 NSCLC 一线治疗中的作用尚不清楚。因此，我们进行了一项系统评价和荟萃分析，以比较 ICI 治疗晚期 NSCLC 的疗效和安全性。
从建库到 2018 年 4 月 30 日，我们检索了 PubMed、Cochrane 中央对照试验注册库和美国临床肿瘤学会数据库，检索比较单药程序性死亡蛋白 1/程序性死亡配体 1 抑制剂（nivolumab、pembrolizumab 或 atezolizumab）或细胞毒性 T 淋巴细胞相关抗原 4 抑制剂（ipilimumab）与化疗在 NSCLC 患者中的疗效的随机对照试验。采用 Review Manager（RevMan 版本 5.3）软件对无进展生存期、总生存期、客观缓解率和不良事件进行荟萃分析。
排除不符合条件的研究后，纳入了 12 项符合条件的随机对照试验。数据显示，ICI 可显著改善无进展生存期（HR 0.66，95%CI 0.57-0.77，P < 0.00001）、总生存期（HR 0.77，95%CI 0.64-0.91，P = 0.003），但不改善客观缓解率（RR 1.97，95%CI 1.25-3.13，P = 0.004），在所有未选择的 NSCLC 人群中。然而，它们未能增加 PD-L1 = 1-49%亚组的 OS（HR 0.78，95%CI 0.51-1.19，P = 0.25）和 PD-L1<1%亚组的 PFS（HR 0.85；95%CI 0.70 至 1.03，P=0.09），ICIs+化疗组优于化疗组。同时，PD-L1 =1-49%亚组的 OS（HR 0.92；95%CI 0.77-1.10，P=0.36）和 PD-L1≥50%亚组的 PFS（HR 0.76；95%CI 0.52-1.11，P=0.15）在 ICI 组和化疗组之间无显著差异。此外，ICI 组的不良事件发生率低于对照组。
ICI 总体上比化疗更耐受。我们的结果为 ICI 的有利风险/效益比提供了进一步的证据支持。
