The Relative Risk of Immune-Related Liver Dysfunction of PD-1/PD-L1 Inhibitors Versus Chemotherapy in Solid Tumors: A Meta-Analysis of Randomized Controlled Trials
机构：[1]School of Medicine, University of Electronic Science and Technology of China, Chengdu, China,四川省人民医院[2]Department of Hepatobiliary Surgery and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, China,四川省人民医院[3]Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China,[4]Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China,四川省人民医院四川省肿瘤医院[5]Department of Radiological Protection, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China
Background: Immune checkpoint inhibitors (ICIs) have made a significant breakthrough in the treatment of solid tumors; however, their use also generates unique immune-related adverse effects (irAEs). Here, we performed a systematic review and meta-analysis to assess the risk of immune-related liver dysfunction between in patients treated by programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors exclusively and chemotherapy. Methods: A comprehensive search of multiple databases identified eligible studies, including randomized controlled trials (RCTs) with PD-1/PD-L1 inhibitors exclusively and chemotherapy in patients with different solid tumors was carried out. The elevations of alanine aminotransferase (ALT) and aspartic aminotransferase (AST) were used to evaluate liver dysfunction. The relative risk (RR) and 95% confidence intervals (CI) were calculated and analyzed by Review Manager 5.3 and STATA version 12.0 statistical software. Results: After screening and eligibility assessment, a total of 5638 patients from 12 RCTs were included in our meta-analysis. In comparison with chemotherapy, patients treated with PD-1/PD-L1 inhibitors exclusively showed an increased incidence of all-grade ALT/AST elevations (ALT: RR, 1.52, 95% CI, 1.09-2.13; p = 0.01; AST: RR, 1.96, 95% CI, 1.37-2.81; p = 0.0002). Patients receiving PD-1 inhibitors showed the significantly higher risk of all-grade ALT/AST elevations incidence than those receiving chemotherapy (ALT: RR, 1.47; 95% CI, 1.05-2.07; p = 0.03; AST: RR, 1.90, 95% CI, 1.32-2.73; p = 0.0005). However, no significant difference was found between PD-L1 inhibitor and chemotherapy group. Moreover, for non-small cell lung cancer (NSCLC) and urothelial carcinoma (UC), patients treated with PD-1/PD-L1 inhibitors exclusively exhibited a significant higher risk of all-grade ALT elevation incidence (NSCLC: RR, 1.92; 95% CI, 1.23-3.02; p = 0.004; UC: RR, 3.36; 95% CI, 1.12-10.06, p = 0.03) and all-grade AST elevation incidence (NSCLC: RR, 2.37; 95% CI, 1.45-3.87, p = 0.0005; UC: RR, 4.47; 95% CI, 1.30-15.38, p = 0.02) than chemotherapy. Conclusions: The meta-analysis confirms that PD-1/PD-L1 inhibitors exclusive pose an increased risk of immune-related liver dysfunction than chemotherapy. PD-1/PD-L1 blockade in NSCLC and UC increase the risk of immune-related liver dysfunction, but not in melanoma (MM) and head-neck squamous cell carcinoma (HNSCC).
基金：
Granting agency: Sichuan Science and Technology Department [2017HH0096, 2019YFH0073]
第一作者机构：[1]School of Medicine, University of Electronic Science and Technology of China, Chengdu, China,
通讯作者：
通讯机构：[4]Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China,[5]Department of Radiological Protection, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China
推荐引用方式(GB/T 7714)：
Deng Siyao,Yang Qinyan,Shu Xiaochen,et al.The Relative Risk of Immune-Related Liver Dysfunction of PD-1/PD-L1 Inhibitors Versus Chemotherapy in Solid Tumors: A Meta-Analysis of Randomized Controlled Trials[J].FRONTIERS IN PHARMACOLOGY.2019,10:doi:10.3389/fphar.2019.01063.
APA：
Deng, Siyao,Yang, Qinyan,Shu, Xiaochen,Lang, Jinyi&Lu, Shun.(2019).The Relative Risk of Immune-Related Liver Dysfunction of PD-1/PD-L1 Inhibitors Versus Chemotherapy in Solid Tumors: A Meta-Analysis of Randomized Controlled Trials.FRONTIERS IN PHARMACOLOGY,10,
MLA：
Deng, Siyao,et al."The Relative Risk of Immune-Related Liver Dysfunction of PD-1/PD-L1 Inhibitors Versus Chemotherapy in Solid Tumors: A Meta-Analysis of Randomized Controlled Trials".FRONTIERS IN PHARMACOLOGY 10.(2019)
