Department of Pharmacy, Harbin Medical University Cancer Hospital, No.150 Ha Ping Road, Harbin, 150040, Heilongjiang, China.
Eur J Clin Pharmacol. 2021 Aug;77(8):1079-1088. doi: 10.1007/s00228-020-03083-9. Epub 2021 Feb 10.
Programmed cell death-1 (PD-1) and programmed cell death ligand-1(PD-L1) inhibitor therapy have been approved for the treatment of many cancers, although their incidence of some side effects was high. We aim to fully investigate the incidence risk of PD-1/PD-L1 inhibitors-related pneumonia and diarrhea in NSCLC patients, as well as treatment-related deaths.
PubMed, Medline, Cochrane Library, and Clinical trials.gov databases were searched up to Sep 17, 2020, for clinical trials of PD-1 inhibitors and PD-L1 inhibitors in the treatment of NSCLC. Randomized controlled trials and their references were screened.
Seventeen trials were included in our meta-analysis, including 11,363 patients. PD-1/PD-L1 inhibitors significantly increased the risk of developing all-grade and high-grade (grade ≥ 3) pneumonia (risk ratio [RR] = 2.28; 95% CI: 1.39-3.76; P < 0.01; RR = 2.38; 95% CI: 1.72-3.29; P < 0.01, respectively). The use of PD-1/PD-L1 inhibitor did not increase the risk of developing all-grade and high-grade diarrhea (RR = 0.79; 95% CI: 0.62-1.01; P = 0.06; RR = 0.96; 95% CI: 0.70-1.31; P = 0.78, respectively). There was no significant difference between the rate of death in PD-1 and PD-L1 inhibitors (P = 0.079).
These data suggest that PD-1/PD-L1 inhibitors significantly increase the risk of all-grade and high-grade pneumonia in NSCLC patients and PD-1/PD-L1 monotherapy increases the risk of all-grade pneumonia in NSCLC patients compared to PD-1/PD-L1 inhibitor combination regimens. Physicians should pay more attention to NSCLC patients who treated with PD-1/PD-L1 inhibitors.
程序性细胞死亡蛋白-1（PD-1）和程序性细胞死亡配体-1（PD-L1）抑制剂已被批准用于治疗多种癌症，尽管它们的一些副作用发生率较高。我们旨在全面研究 PD-1/PD-L1 抑制剂相关肺炎和非小细胞肺癌（NSCLC）患者腹泻的发生率风险，以及与治疗相关的死亡率。
检索了 PubMed、Medline、Cochrane 图书馆和 Clinical trials.gov 数据库，截至 2020 年 9 月 17 日，以获取 PD-1 抑制剂和 PD-L1 抑制剂治疗 NSCLC 的临床试验。筛选随机对照试验及其参考文献。
我们的荟萃分析纳入了 17 项试验，共纳入 11363 例患者。PD-1/PD-L1 抑制剂显著增加了所有级别和高级别（≥3 级）肺炎的发生风险（风险比 [RR] = 2.28；95%置信区间：1.39-3.76；P < 0.01；RR = 2.38；95%置信区间：1.72-3.29；P < 0.01）。使用 PD-1/PD-L1 抑制剂不会增加所有级别和高级别腹泻的发生风险（RR = 0.79；95%置信区间：0.62-1.01；P = 0.06；RR = 0.96；95%置信区间：0.70-1.31；P = 0.78）。PD-1 和 PD-L1 抑制剂的死亡率之间无显著差异（P = 0.079）。
这些数据表明，PD-1/PD-L1 抑制剂显著增加 NSCLC 患者的所有级别和高级别肺炎的发生风险，与 PD-1/PD-L1 抑制剂联合治疗方案相比，PD-1/PD-L1 单药治疗增加了 NSCLC 患者的所有级别肺炎的发生风险。医生应更加关注接受 PD-1/PD-L1 抑制剂治疗的 NSCLC 患者。
