Impact of PD-L1 expression, driver mutations and clinical characteristics on survival after anti-PD-1/PD-L1 immunotherapy versus chemotherapy in non-small-cell lung cancer: A meta-analysis of randomized trials
Impact of PD-L1 expression, driver mutations and clinical characteristics on survival after anti-PD-1/PD-L1 immunotherapy versus chemotherapy in non-small-cell lung cancer: A meta-analysis of randomized trials
复制标题
DOI：
10.1080/2162402x.2017.1396403
复制
发表时间：
2018-12-02
期刊：
影响因子：
7.2
通讯作者：
Stebbing, Justin
中科院分区：
文献类型：
--
作者：
Huang, Qingyuan;Zhang, Hua;Stebbing, Justin
目的：探讨程序性死亡配体1 （programmed death-ligand 1, PD-L1）表达、致癌突变和临床特征对非小细胞肺癌（NSCLC）患者抗pd -1/PD-L1抗体治疗与化疗后生存率的影响。患者和方法：这项荟萃分析包括比较抗pd -1/PD-L1抗体与化疗的随机试验。提取试验人群和预先指定的亚组的总生存期（OS）的风险比（hr）和95%置信区间（CI）。在适当的情况下，我们使用固定效应或随机效应模型计算治疗效果的汇总估计。所有统计检验均为双侧检验。结果：纳入7项试验，共3871例患者。综合结果显示，与化疗相比，抗pd -1/PD-L1免疫治疗显著延长了OS （HR: 0.73; 95% CI, 0.63 ~ 0.84）和PFS （HR: 0.84; 95% CI, 0.71 ~ 0.99）。在所有PD-L1表达亚组中均观察到免疫治疗的OS获益（阴性：HR， 0.79; 95% CI， 0.67至0.93；弱阳性：HR， 0.80; 95% CI， 0.67至0.95；强阳性：HR， 0.61; 95% CI， 0.47至0.78）。与弱阳性PD-L1表达相比，强阳性PD-L1表达有更多获益的趋势（相互作用P = 0.08）。KRAS突变亚组（HR: 0.60; 95% CI， 0.39至0.93）、EGFR野生型亚组（HR: 0.73; 95% CI， 0.61至0.87）和吸烟者亚组（HR: 0.70; 95% CI， 0.60至0.83）与相应亚组相比，免疫治疗获得了显著的OS获益。免疫治疗的生存获益与组织学、中枢神经系统转移、年龄、性别和运动状态无显著相关。结论：本研究证实，与化疗相比，抗pd -1/PD-L1治疗可提高总生存期。无论PD-L1表达水平如何，均可观察到益处；然而，PD-L1强阳性患者倾向于获得最大的益处。与KRAS野生型或EGFR突变型NSCLC相比，KRAS突变型或EGFR突变型肿瘤患者分别从免疫治疗中获得了更高的生存获益。
Purpose: To investigate the impact of programmed death-ligand 1 (PD-L1) expression, oncogenic mutations, and clinical characteristics on survival after treatment with anti-PD-1/PD-L1 antibodies versus chemotherapy in non-small cell lung cancer (NSCLC). Patients and Methods: This meta-analysis included randomized trials comparing anti-PD-1/PD-L1 antibodies with chemotherapy. Hazard ratios (HRs) and 95% confidence interval (CI) for overall survival (OS) for the trial population and prespecified subgroups were extracted. We calculated pooled estimates of treatment efficacy using the fixed-effects or random-effects model when appropriate. All statistical tests were two sided. Results: Seven trials involving 3871 patients were included. The pooled results showed that anti-PD-1/PD-L1 immunotherapy significantly prolonged OS (HR: 0.73; 95% CI, 0.63 to 0.84) and PFS (HR: 0.84; 95% CI, 0.71 to 0.99) compared to chemotherapy. OS benefit from immunotherapy were observed in all PD-L1 expression subgroups (negative: HR, 0.79; 95% CI, 0.67 to 0.93; weak-positive: HR, 0.80; 95% CI, 0.67 to 0.95; strong-positive: HR, 0.61; 95% CI, 0.47 to 0.78). Strong-positive PD-L1 expression showed a trend towards more benefit compared to weak-positive PD-L1 expression (interaction P = 0.08). KRAS mutant (HR: 0.60; 95% CI, 0.39 to 0.93), EGFR wild-type (HR: 0.73; 95% CI, 0.61 to 0.87) and smoker (HR: 0.70; 95% CI, 0.60 to 0.83) subgroups achieved significant OS benefit from immunotherapy compared to corresponding subgroups. Survival benefit to immunotherapy was not significantly associated with histology, CNS metastases, age, gender and performance status. Conclusion: This study confirmed that treatment with anti-PD-1/PD-L1 improves overall survival compared with chemotherapy. Benefit was seen, regardless of PD-L1 expression levels; however, PD-L1 strong-positive patients trended to have greatest benefit. Patients with a KRAS mutant or EGFR wild-type tumor have improved survival benefit from immunotherapy compared with KRAS wild-type or EGFR mutant NSCLC, respectively.