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Systematic Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00972

Comparative safety of PD-1/PD-L1 inhibitors for cancer patients: systematic review and network meta-analysis

 Yafang Huang1*, Wenjie Xie2,  Haiyu Fan1 and Juan Du1
  • 1Capital Medical University, China
  • 2University of Bern, Switzerland

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 (14204 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%). Using PD-1/PD-L1 inhibitors alone were 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.

Keywords: PD-1 inhibitor, PD-L1 inhibitor, Treatment-related adverse events, Immune-related adverse events, Network meta-analysis (NMA)

Received: 23 May 2019; Accepted: 13 Sep 2019.

Copyright: © 2019 Huang, Xie, Fan and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Yafang Huang, Capital Medical University, Beijing, Beijing Municipality, China,