%0 Figure %A Huang, Ya-fang %A Xie, Wen-jie %A Fan, Hai-yu %A Du, Juan %D 2019 %T Image_3_Comparative Safety of PD-1/PD-L1 Inhibitors for Cancer Patients: Systematic Review and Network Meta-Analysis.TIF %U https://frontiersin.figshare.com/articles/figure/Image_3_Comparative_Safety_of_PD-1_PD-L1_Inhibitors_for_Cancer_Patients_Systematic_Review_and_Network_Meta-Analysis_TIF/9923054 %R 10.3389/fonc.2019.00972.s003 %2 https://frontiersin.figshare.com/ndownloader/files/17852750 %K PD-1 inhibitors %K PD-L1 inhibitors %K treatment-related adverse events %K immune-related adverse events %K network meta-analysis %X

Background: Comprehensive evidence comparing treatment-related adverse events (trAEs) among PD-1/PD-L1 inhibitors is unavailable.

Methods: A systematic review and network meta-analysis (NMA) was conducted. Randomized controlled trials in cancer patients treated with PD1/PD-L1 inhibitors or their combinations with chemotherapy/placebo and compared with PD1/PD-L1 inhibitors/chemotherapy/placebo were identified through comprehensive searches of multiple databases. Bayesian NMA was performed using random-effects model. Relative ranking of treatments was assessed with surface under the cumulative ranking (SUCRA) probabilities. Incidences and odds ratios of trAEs and immune-related adverse events (irAEs) of all-grade (Grade 1–5) and high-grade (Grade 3–5) were estimated.

Results: Twenty-three RCTs (14,204 patients) comparing six different strategies were included. The incidence of trAEs was lowest for PD-L1 inhibitors (all-grade: pooled incidence = 60.4%, SUCRA = 77.2%; high-grade: 6.4, 73.8%). PD-L1 inhibitors plus chemotherapy had the highest incidence of all-grade trAEs (88.6, 10.1%), while PD-1 inhibitors plus chemotherapy had the highest incidence of high-grade trAEs (8.2, 9.3%). The use of PD-1/PD-L1 inhibitors alone was associated with significant reductions on high-grade trAEs, compared with PD-1/PD-L1 inhibitors plus chemotherapy. PD-1 inhibitors had the highest incidence of irAEs (all-grade: 15.1, 9.5%; high-grade: 3.5, 16.8%). Compared with PD-L1 inhibitors, PD-1 inhibitors neither increased trAEs nor irAEs significantly. Results from sensitivity analyses were consistent.

Conclusions: Current data showed that PD-L1 inhibitors had the best safety on both trAEs and irAEs. Awareness of the comparative safety could promote further appropriate utilization of PD-1/PD-L1 inhibitors in clinical practice.

%I Frontiers