Da Lijun, Teng Yuanjun, Wang Na, Zaguirre Karen, Liu Yating, Qi Yali, Song Feixue
Department of Oncology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, China.
Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, China.
Front Pharmacol. 2020 Jan 30;10:1671. doi: 10.3389/fphar.2019.01671. eCollection 2019.
Although combination therapy with immune checkpoint inhibitors (ICIs) provides a promising efficacy in multiple cancers, their use is facing challenges for a high incidence of adverse effects. This meta-analysis was conducted to compare the risks of organ-specific immune-related adverse events (IRAEs) associated with ICI monotherapy versus combination therapy among cancer patients.
Electronic databases were systematically searched to include eligible randomized controlled trials (RCTs). Any-grade and 3-5 grade IRAEs (colitis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism, and hypophysitis) were extracted for meta-analysis. Two reviewers independently assessed the methodological quality. The RevMan 5.3.5 software was used for meta-analysis.
A total of 10 studies involving 8 RCTs with 2716 patients were included in this study. The most common any-grade adverse event was colitis (14.5%), followed by hypothyroidism (13.8%), hepatitis (10.4%), hypophysitis (10.0%), hyperthyroidism (9.3%), and pneumonitis (4.6%). Meta-analysis showed that ICI combination therapy significantly increased the risks of any-grade IRAEs in colitis [relative risk (RR), 3.56; 95% confidence interval (CI), 1.56-8.12; < 0.05], pneumonitis (RR, 2.31; 95% CI, 1.54-3.45; < 0.05), hepatitis (RR, 2.54; 95% CI, 1.65-3.91; < 0.05), hypothyroidism (RR, 2.17; 95% CI, 1.71-2.76; < 0.05), hyperthyroidism (RR, 3.13; 95% CI, 2.08-4.70; < 0.05), and hypophysitis (RR, 3.54; 95% CI, 2.07-6.07; < 0.05) compared with ICI monotherapy, as well as 3-5 grade IRAEs in colitis (RR, 2.50; 95% CI, 1.62-3.86; < 0.05), pneumonitis (RR, 1.99; 95% CI, 1.00-3.93; = 0.05), and hepatitis (RR, 2.70; 95% CI, 1.29-5.63; < 0.05).
This meta-analysis demonstrated that, compared with ICI monotherapy, patients receiving ICI combination therapy significantly increased organ-specific IRAEs in colitis, hypothyroidism, hepatitis, hypophysitis, hyperthyroidism, and pneumonitis. The incidence and severity of organ-specific IRAEs were drug and dose independent.
尽管免疫检查点抑制剂（ICI）联合疗法在多种癌症中显示出有前景的疗效，但其使用因不良反应高发而面临挑战。本荟萃分析旨在比较癌症患者中ICI单药治疗与联合治疗相关的器官特异性免疫相关不良事件（IRAEs）风险。
系统检索电子数据库以纳入符合条件的随机对照试验（RCT）。提取任何级别和3 - 5级IRAEs（结肠炎、肺炎、肝炎、甲状腺功能减退、甲状腺功能亢进和垂体炎）进行荟萃分析。两名研究者独立评估方法学质量。使用RevMan 5.3.5软件进行荟萃分析。
本研究共纳入10项研究，涉及8项RCT，共2716例患者。最常见的任何级别不良事件是结肠炎（14.5%），其次是甲状腺功能减退（13.8%）、肝炎（10.4%）、垂体炎（10.0%）、甲状腺功能亢进（9.3%）和肺炎（4.6%）。荟萃分析显示，与ICI单药治疗相比，ICI联合治疗显著增加了结肠炎（相对风险[RR]，3.56；95%置信区间[CI]，1.56 - 8.12；P < 0.05）、肺炎（RR，2.31；95% CI，1.54 - 3.45；P < 0.05）、肝炎（RR，2.54；95% CI，1.65 - 3.91；P < 0.05）、甲状腺功能减退（RR，2.17；95% CI，1.71 - 2.76；P < 0.05）、甲状腺功能亢进（RR，3.13；95% CI，2.08 - 4.70；P < 0.05）和垂体炎（RR，3.54；95% CI，2.07 - 6.07；P < 0.05）中任何级别IRAEs的风险，以及结肠炎（RR，2.50；95% CI，1.62 - 3.86；P < 0.05）、肺炎（RR，1.99；95% CI，1.00 - 3.93；P = 0.05）和肝炎（RR，2.70；95% CI，1.29 - 5.63；P < 0.05）中3 - 5级IRAEs的风险。
本荟萃分析表明，与ICI单药治疗相比，接受ICI联合治疗的患者在结肠炎、甲状腺功能减退、肝炎、垂体炎、甲状腺功能亢进和肺炎中器官特异性IRAEs显著增加。器官特异性IRAEs的发生率和严重程度与药物及剂量无关。
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