The overall safety evaluation of programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) treatment for lung cancer patients; An updated systematic review and meta-analysis

Abstract

Background:We performed the meta-analysis to evaluate the overall safety of programmed cell death-1 (PD-1) or ligand 1 (PD-L1) inhibitor treatment for lung cancer patients. Method:Randomized controlled trials were collected according to the Preferred Reporting Items for Systematic Reviews and Metaanalyses (PRISMA) guidelines. Risk ratio (RR) of PD-1/PD-L1 inhibitor treatment-related death, treatment-related adverse events, any serious events, and any events leading to discontinuation were all taken into account for the final evaluation. Results: Fourteen studies were collected for the meta-analysis. The RR of treatment-related death for PD-1/PD-L1 was significantly lower than that of the control group (RR=0.37, 95% confidence interval, CI: [0.21, 0.66]). Similar analysis results could also be seen for the RR of treatment-related adverse events and adverse events leading to discontinuation. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation (RR=1.68, 95% CI: [1.22, 3.32]). The RR of overall treatment-related adverse events was lower in nivolumab (PD-1) than that of the control group (nivolumab+ipilimumab) (RR= 0.77, 95% CI: [0.65, 0.90]). Similar analysis results could also be seen in the RR of treatment-related adverse events for grade 3 to 5 and adverse events leading to discontinuation. Conclusion: Compared with chemotherapy, RR of the treatment-related deaths associated with PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while it did not increase the RR when they were combined with chemotherapy or other drugs. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation. Abbreviations: CI = confidence interval, NSCLC = non-small cell lung cancer, PD-1 = programmed cell death-1, PD-L1 = programmed cell death ligand 1, PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses, RR = risk ratio, SCLC = small cell cancer.