J Cancer 2018; 9(9):1614-1622. doi:10.7150/jca.24200

Research Paper

Risk of immune-related colitis with PD-1/PD-L1 inhibitors vs chemotherapy in solid tumors: systems assessment

Qiang Su1, Xiaochen Zhang2, Xinhua Shen3, Yanli Hou1✉, Zhigang Sun4✉, Zu Hua Gao5,6✉

1. Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China; Department of Pathology, Research Institute of McGill University Health Center, Montreal, Quebec, Canada
2. Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China
3. Department of Biomedical Engineering of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College
4. Department of Thoracic Surgery, Jinan Center Hospital Affiliated to Shandong University, Shandong University, Jinan, 250014, China
5. Department of Pathology, Research Institute of McGill University Health Center, Montreal, Quebec, Canada
6. Liaocheng City Hospital, Shandong Province, PR China

Abstract

Background: We performed a meta-analysis to evaluate the risk of immune-related colitis associated with PD1/PD-L1 inhibitors as compared to chemotherapy in solid tumor patients.

Methods: Eligible studies were identified through a comprehensive search of multiple databases and included solid tumor patients in randomized controlled trials (RCTs) with PD-1/PD-L1 inhibitors. The data was analyzed by Stata version 12.0 software.

Results: After exclusion of ineligible studies, 11 clinical trials were considered eligible for the meta-analysis, including 5751 patients. Compared with chemotherapy, the risk ratios (RRs) of all-grade colitis were significant for the PD-1 inhibitor subgroup (RR 2.69, 95% confidence interval (CI): 1.15-6.29, p=0.023), and for pembrolizumab subgroup (RR 3.17, 95% CI: 1.08-9.37, p=0.037), but not for nivolumab treatment and PD-L1 inhibitor (atezolizumab) treatment (RR 2.05, 95% CI: 0.52-8.13, p=0.305; RR 4.75,95% CI: 0.56-40.50, p=0.154, respectively). The RR of all-grade colitis was significant for PD-1/PD-L1 inhibitor in NSCLC (RR 4.34, 95% CI: 1.37-13.82, p=0.013), and not significant in melanoma (RR 2.11, 95% CI: 0.54-8.34, p=0.285). Moreover, the RRs of all-grade diarrhea were significant for the PD-1 inhibitor subgroup (RR 0.61, 95% CI: 0.44-0.83, p=0.002), for the nivolumab subgroup (RR 0.54, 95% CI: 0.34-0.87, p=0.012), and for atezolizumab subgroup (RR 0.48, 95% CI: 0.25-0.89, p=0.021). The RR of high-grade diarrhea was significant for atezolizumab subgroup (RR 0.34, 95% CI: 0.12-0.94, p=0.037).

Conclusions: Our meta-analysis demonstrates that compared with chemotherapy, pembrolizumab may result in a higher risk of all-grade immune-mediated colitis. PD-1/PD-L1 inhibitor treatment in NSCLC patients, but not in melanoma patients, increases the risk of all-grade colitis incidence.

Keywords: Immune-related colitis, PD-1, PD-L1, Cancer, Meta-analysis

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Su Q, Zhang X, Shen X, Hou Y, Sun Z, Gao ZH. Risk of immune-related colitis with PD-1/PD-L1 inhibitors vs chemotherapy in solid tumors: systems assessment. J Cancer 2018; 9(9):1614-1622. doi:10.7150/jca.24200. Available from http://www.jcancer.org/v09p1614.htm