Shanghai Cancer Center and Shanghai Medical College, Fudan University, Shanghai, China.
Department of Clinical Biochemistry, School of Public Health Taishan Medical University, Taian, China.
Mol Cancer Ther. 2017 Aug;16(8):1588-1595. doi: 10.1158/1535-7163.MCT-17-0155. Epub 2017 Apr 26.
Pneumonitis, a rare but potentially life-threatening adverse event in cancer patients receiving programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors, has been reported in case reports, clinical trials, and retrospective studies. We performed a systematic review and meta-analysis to calculate the RR of pneumonitis associated with the use of PD-1/L1 inhibitors in randomized clinical trials (RCT). We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant RCTs comparing PD-1/L1 inhibitors to control with available data on pneumonitis. The pooled incidence, RR, and 95% confidence intervals (CI) were calculated using fixed effects or random effects model according to the heterogeneity of included trials. Twelve RCTs were eligible for the meta-analysis, yielding a total of 5,775 patients included in trials evaluating a PD-1 inhibitor; no eligible trials evaluated a PD-L1 inhibitor. The pooled incidence of all-grade pneumonitis for patients treated with PD-1 inhibitors was 3.2% (95% CI, 2.3-4.5), and that of high-grade pneumonitis was 1.1% (95% CI, 0.7-1.7). The RR of all-grade and high-grade pneumonitis was 4.36 (95% CI, 2.58-7.38) and 2.86 (95% CI, 1.30-6.31), respectively. In a sensitivity analysis, PD-1 inhibitors were also associated with significantly increased risk of pneumonitis per person-month (for all grade, RR = 3.37; 95% CI, 1.97-5.76; for high grade, RR = 2.25; 95% CI, 1.03-4.94). PD-1 inhibitors were associated with a significant increase of all-grade and high-grade pneumonitis both per treatment episode and per person-month. .
间质性肺病是一种罕见但可能危及生命的不良事件，在接受程序性死亡受体 1（PD-1）或程序性死亡配体 1（PD-L1）抑制剂治疗的癌症患者中已有病例报告、临床试验和回顾性研究报道。我们进行了系统评价和荟萃分析，以计算随机临床试验（RCT）中使用 PD-1/L1 抑制剂与间质性肺病相关的 RR。我们检索了 MEDLINE、Embase、Cochrane 对照试验中心注册库、试验登记处、会议录、综述文章和试验出版物的参考文献，以获取所有比较 PD-1/L1 抑制剂与对照药物且有间质性肺病数据的相关 RCT。使用固定效应或随机效应模型根据纳入试验的异质性计算总发生率、RR 和 95%置信区间（CI）。12 项 RCT 符合荟萃分析标准，共纳入 5775 例接受 PD-1 抑制剂治疗的患者；没有符合条件的试验评估 PD-L1 抑制剂。接受 PD-1 抑制剂治疗的患者发生所有级别间质性肺病的总发生率为 3.2%（95%CI，2.3-4.5），发生 3 级及以上间质性肺病的发生率为 1.1%（95%CI，0.7-1.7）。所有级别和 3 级及以上间质性肺病的 RR 分别为 4.36（95%CI，2.58-7.38）和 2.86（95%CI，1.30-6.31）。在敏感性分析中，每个治疗周期 PD-1 抑制剂与间质性肺病的风险也显著增加（所有级别，RR=3.37；95%CI，1.97-5.76；3 级及以上，RR=2.25；95%CI，1.03-4.94）。PD-1 抑制剂与每个治疗周期和每个治疗周期的所有级别和 3 级及以上间质性肺病的风险显著增加有关。
