A Systematic Review and Meta-Analysis of Immune-Related Adverse Events of Anti-PD-1 Drugs in Randomized Controlled Trials. (19th October 2020)

• Record Type: Journal Article
• Authors: Wang, Yukun; Kong, Dejiu; Wang, Chaokun; Chen, Jing; Li, Jing; Liu, Zhiwei; Li, Xinyang; Wang, Ziming; Yao, Ge; Wang, Xinshuai
• Is Part Of: Technology in cancer research & treatment. Volume 19(2020)
• Publication Date: 2020-10-19
• Subjects: anti-PD-1 drugs -- immune-related adverse events -- systematic review -- meta-analysis; Oncology -- Periodicals; Cancer -- Diagnosis -- Periodicals; Cancer -- Treatment -- Technological innovations -- Periodicals; 616.994
• DOI: 10.1177/1533033820967454
• Languages: English
• ISSNs: 1533-0346

Abstract

Objective: We aimed to evaluate immune-related adverse events occurring in clinical trials of anti-programmed cell death 1 (PD-1) drugs, compared with control treatments, including chemotherapy, targeted drugs, or placebo. Further we compared the occurrence of immune -related events in patients treated with different anti-PD-1 drugs. Data Sources: Randomized controlled trial (RCT) data were sourced from PubMed, Embase, and the Cochrane Central Register of Controlled Trials combined withhttps://clinicaltrials.gov . Methods: Randomized controlled trial of anti-PD-1 drugs compared with control treatments published between January 1, 1970 and March 1, 2019, were searched and data on trial patient characteristics, and adverse events extracted, reviewed, and subjected to meta-analysis. Results: Eighteen Randomized controlled trials were included in our study. The Randomized controlled trials compared nivolumab (n = 12), pembrolizumab (n = 6), with chemotherapy (n = 13), targeted drugs (n = 2), or placebo (n = 3). Compared with the control group, the risk of any immune-related adverse events in patients treated with anti-PD-1 drugs was increased (RR, 2.65; 95% confidence interval, 1.84–3.83; P < 0.00001). Of the immune-related adverse events, the risk rates of pneumonitis (risk ratio, 2.10; 95% CI, 0.85-5.18), colitis (2.96;1.62-5.38), hypophysitis(4.79;1.54-14.89), hypothyroidism(7.87;5.36-11.57), hyperthyroidism (7.03;4.35-11.34), rash (1.58;0.98-2.54), pruritus (2.28; 1.38-3.76), and hepatitis (9.31;2.18-39.85) were increased by anti-PD-1 drugs. Further, the risk of immune-related adverse events was similar for patients treated with pembrolizumab and nivolumab ( P = 0.14). Conclusions: In addition to previously reported organ-specific immune-related adverse events, we found that the risk of hyperthyroidism was also increased, in anit-PD-1-treated patients, relative to control treatments. The risk of total immune-related adverse events, was similar for pembrolizumab and nivolumab.