Huo Geng-Wei, Zhu Fu-Yi, Zuo Ran, Song Ying, Chen Wei-Dong, Chen Wen-Ming, Zhang Hong-Mei, Jia Sha-Sha, Chen Peng
Department of Thoracic Oncology, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Departmentof Oncology, Jining No. 1 People's Hospital, Jining, China.
Transl Cancer Res. 2021 Jul;10(7):3389-3403. doi: 10.21037/tcr-21-125.
We conducted a meta-analysis to evaluates the incidence of the gastrointestinal (GI) adverse events with the use of PD-1 inhibitors among patients with advanced non-small cell lung cancer (NSCLC).
The PICOs (participants, intervention, comparison, and outcomes) elements were used for the selection of studies to meet the inclusion and exclusion criteria. Google Scholar, PubMed, Science Direct and proceedings of major oncology conferences were systematically searched from their inception to December 2020, to identify studies which reported the GI adverse events of PD-1 inhibitors among patients with NSCLC. Risks of bias were assessed by using a revised methodological index for nonrandomized studies (MINORS). Pooled incidences and weighted relative risk (RR) estimate for GI adverse events, the incidence of treatment discontinuation due to GI adverse events was also calculated. To perform the analysis of qualified studies, the model of random effects was used and the inconsistency of studies with the I2 index was investigated. OpenMeta 10.10, Stata 11.0 and RevMan 5.3 software were used for data analysis.
The research included 15 studies comprising of a total of 3,716 patients. The incidences of all-grade GI symptoms were: diarrhea 8.6% (95% CI: 6.6-10.6%), nausea 9.2% (95% CI: 7.3-11.0%), vomiting 3.2% (95% CI: 1.9-4.5%), constipation 2.8% (95% CI: 1.8-3.9%), colitis 0.7% (95% CI: 0.4-1.1%), stomatitis (95% CI: 1.0-2.7%), and decreased appetite 10.0% (95% CI: 8.3-11.7%). Therapy using PD-1 inhibitors was discontinued in 2.5% (95% CI: 0.0-5.1%) of patients with nausea, in 3.0% (95% CI: 0.7-5.3%) of those with diarrhea, and in 45.7% (95% CI: 20.6-70.7%) of patients with colitis. Compared with chemotherapy, the use of PD-1 inhibitors showed significant increase in the occurrence of grade 1-4 colitis (RR =3.90, 95% CI: 1.41-10.81, P=0.009) and grade 3-4 colitis (RR =3.76, 95% CI: 1.07-13.26, P=0.04).
This meta-analysis provides a reliable estimate of the incidences of GI adverse events among NSCLC patients. Especially when colitis does occur, it often results in therapy discontinuation. Use of PD-1 inhibitors led to a higher incidence of colitis as compared to the use of chemotherapy.
我们进行了一项荟萃分析，以评估晚期非小细胞肺癌（NSCLC）患者使用PD - 1抑制剂时胃肠道（GI）不良事件的发生率。
采用PICOs（参与者、干预措施、对照和结局）要素来选择符合纳入和排除标准的研究。对谷歌学术、PubMed、科学Direct以及主要肿瘤学会议论文集进行系统检索，检索时间从其创建至2020年12月，以确定报告NSCLC患者中PD - 1抑制剂胃肠道不良事件的研究。使用修订后的非随机研究方法学指数（MINORS）评估偏倚风险。计算GI不良事件的合并发生率和加权相对风险（RR）估计值，还计算了因GI不良事件导致治疗中断的发生率。为了对合格研究进行分析，使用随机效应模型并通过I2指数研究研究间的不一致性。使用OpenMeta 10.10、Stata 11.0和RevMan 5.3软件进行数据分析。
该研究纳入了15项研究，共3716例患者。所有级别的GI症状发生率分别为：腹泻8.6%（95%置信区间：6.6 - 10.6%），恶心9.2%（95%置信区间：7.3 - 11.0%），呕吐3.2%（95%置信区间：1.9 - 4.5%），便秘2.8%（95%置信区间：1.8 - 3.9%），结肠炎0.7%（95%置信区间：0.4 - 1.1%），口腔炎（95%置信区间：1.0 - 2.7%），食欲减退10.0%（95%置信区间：8.3 - 11.7%）。因恶心而停药的患者占2.5%（95%置信区间：0.0 - 5.1%），因腹泻而停药的患者占3.0%（95%置信区间：0.7 - 5.3%），因结肠炎而停药的患者占45.7%（95%置信区间：20.6 - 70.7%）。与化疗相比，使用PD - 1抑制剂导致1 - 4级结肠炎（RR = 3.90，95%置信区间：1.41 - 10.81，P = 0.009）和3 - 4级结肠炎（RR = 3.76，95%置信区间：1.07 - 13.26，P = 0.04）的发生率显著增加。
这项荟萃分析提供了NSCLC患者中GI不良事件发生率的可靠估计。特别是当结肠炎确实发生时，它常常导致治疗中断。与化疗相比，使用PD - 1抑制剂导致结肠炎的发生率更高。
