Yu Xiaolin, Zhang Xiaomei, Yao Ting, Zhang Ye, Zhang Yanxia
Graduate School, Beijing University of Chinese Medicine, Beijing, China.
Department of Respiratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
Front Med (Lausanne). 2021 Feb 15;8:627089. doi: 10.3389/fmed.2021.627089. eCollection 2021.
Immune checkpoint inhibitors (ICIs) have previously been reported to have a promising potential in terms of the improvement of outcomes in non-small cell lung cancer (NSCLC). Fatal adverse events (FAEs) of ICIs are relatively uncommon, and the incidence and risk in NSCLC remain unclear. In the present study, we conducted a systematic review and meta-analysis to evaluate the risk of FAEs in NSCLC patients administered with ICIs. Potentially relevant studies were identified in PubMed, EMBASE, and Cochrane library database from inception to September 16, 2020. The systematic review and meta-analysis included randomized controlled trials that reported treatment-related FAEs in NSCLC. The pooled incidence and risk ratios (RRs) were calculated to evaluate prospective risk. Twenty clinical trials that included a total of 13,483 patients were selected for the meta-analysis. The overall incidence of FAEs was 0.65% [95% confidence interval (CI) = 0.31-1.07, = 50.2%] in ICI monotherapy, 1.17% (95% CI = 0.74-1.69, = 56.3%) in chemotherapy, and 2.01% (95% CI = 1.42-2.69, = 5.9%) in the combination therapy (ICI and chemotherapy). ICI monotherapy was associated with lower incidence of FAEs caused by blood system disorders (RR = 0.23, 95% CI = 0.07-0.73, = 0.013, = 0%) and infectious diseases (RR = 0.29, 95% CI = 0.13-0.63, = 0.002, = 0%). The incidence of pneumonitis significantly increased in immunotherapy (RR = 5.72, 95% CI = 1.14-28.80, = 0.03, = 0%). The results of the present study demonstrate that ICI monotherapy decreases the risk of FAEs, whereas the combined regimens with chemotherapy have the opposite tendency as compared to conventional chemotherapy. While the patients who received chemotherapy suffered the risks of death mainly from myelosuppression and infection, those who received immunotherapy were mainly threatened by immune-related pneumonitis.
免疫检查点抑制剂（ICIs）此前已有报道称，在改善非小细胞肺癌（NSCLC）的治疗结果方面具有广阔前景。ICIs的致命不良事件（FAEs）相对不常见，NSCLC中的发生率和风险仍不清楚。在本研究中，我们进行了一项系统评价和荟萃分析，以评估接受ICIs治疗的NSCLC患者发生FAEs的风险。从数据库建立至2020年9月16日，在PubMed、EMBASE和Cochrane图书馆数据库中检索潜在相关研究。该系统评价和荟萃分析纳入了报告NSCLC中与治疗相关FAEs的随机对照试验。计算合并发病率和风险比（RRs）以评估前瞻性风险。荟萃分析选取了20项临床试验，共纳入13483例患者。ICIs单药治疗中FAEs的总体发生率为0.65%[95%置信区间（CI）=0.31 - 1.07，I² = 50.2%]，化疗组为1.17%（95%CI = 0.74 - 1.69，I² = 56.3%），联合治疗组（ICIs与化疗）为2.01%（95%CI = 1.42 - 2.69，I² = 5.9%）。ICIs单药治疗与血液系统疾病（RR = 0.23，95%CI = 0.07 - 0.73，P = 0.013，I² = 0%）和传染病（RR = 0.29，95%CI = 0.13 - 0.63，P = 0.002，I² = 0%）引起的FAEs发生率较低相关。免疫治疗中肺炎的发生率显著增加（RR = 5.72，95%CI = 1.14 - 28.80，P = 0.03，I² = 0%）。本研究结果表明，ICIs单药治疗可降低FAEs风险，而与传统化疗相比，联合化疗方案有相反趋势。接受化疗的患者死亡风险主要来自骨髓抑制和感染，而接受免疫治疗的患者主要受免疫相关肺炎威胁。
