Objective: This network meta-analysis will provide a complete toxicity profile, toxicity profile, and safety ranking of immune checkpoint inhibitors (ICIs) for treatment of advanced non-small cell lung cancer (NSCLC).Methods: We found 12 phase II or III randomized clinical trials (RCTs) including 8,453 patients with NSCLC by searching Pubmed, Embase, and ClinicalTrials.gov. Risk ratios (RRs) and 95% confidence interval (CI) were used to compare the rate of immune-related adverse events (irAEs) for different ICIs-based treatments using pairwise and network meta-analysis with random effects.Results: For dermatologic irAEs, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab (97.4%), pembrolizumab (80.1%), nivolumab (67.1%), pembrolizumab + platinum (43.3%), atezolizumab + platinum (39.9%), durvalumab (17.5%), platinum-based chemotherapy (4.7%). For colitis, the corresponding ranking of incidences of the six groups from high to low was: atezolizumab + platinum (77.1%), nivolumab (67.3%), pembrolizumab (60.5%), durvalumab (45.2%), pembrolizumab + platinum (41.4%), platinum-based chemotherapy (8.5%). For endocrine irAEs, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab (79.1%), durvalumab (69.1%), pembrolizumab (61.9%), atezolizumab + platinum (60.4%),nivolumab (45.7%), pembrolizumab + platinum (33.5%), platinum-based chemotherapy (0.3%). For pneumonitis, the corresponding ranking of incidences of the seven groups from high to low was: pembrolizumab (99.3%), pembrolizumab + platinum (65.1%), durvalumab (62.2%), atezolizumab + platinum (56%), nivolumab (35.9%), platinum-based chemotherapy (18.1%),atezolizumab (13.3%). For hepatitis, the corresponding ranking of incidences of the six groups from high to low was: pembrolizumab (71.2%), pembrolizumab + platinum (64.3%), durvalumab (56.4%), atezolizumab + platinum (53.8%), nivolumab (44.5%), platinum-based chemotherapy (9.8%).Conlusion: In addition to platinum-based chemotherapy, durvalumab for dermatologic and liver irAEs, pembrolizumab for gastrointestinal irAEs, pembrolizumab + platinum for endocrine irAEs, and atezolizumab for pneumonitis may be associated with lower rates of irAEs than other immune-based regimens. Nivolumab + ipilimumab for dermatologic and endocrine irAEs, atezolizumab + platinum for colitis, and pembrolizumab for pneumonitis and hepatitis may be associated with higher rates of irAEs.

Background In recent years programmed cell death receptor 1 (PD-1) and its ligand, programmed cell death ligand-1 (PD-L1), have opened a new era of advanced non-small cell lung cancer (NSCLC) treatment,while yielding higher rates of immune-related adverse events (irAEs) than platinum-based chemotherapy. This network meta-analysis indirectly compared the incidences of irAEs of PD-1/PD-L1 inhibitor + chemotherapy, PD-1/PD-L1 inhibitor alone, and dual PD-1/PD-L1 inhibitor combinations. Methods We found 12 phase II or III randomized clinical trials (RCTs) including 8,453 patients with NSCLC by searching Pubmed, Embase, and the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov. Summary risk ratios(RRs) and 95% confidence interval were used to compare the rate of irAEs for different ICI-based treatments using pairwise and network meta-analysis with random effects. Results In addition to platinum-based chemotherapy, in terms of dermatologic irAEs, durvalumab had the lowest rate compared to pembrolizumab + platinum, nivolumab, atezolizumab + platinum, nivolumab, pembrolizumab, nivolumab + ipilimumab. In terms of gastrointestinal irAEs, pembrolizumab had the lowest rate compared to nivolumab, nivolumab + ipilimumab, durvalumab, atezolizumab + platinum, and pembrolizumab + platinum. For endocrine irAEs, pembrolizumab + platinum had the lowest rate compared to pembrolizumab, atezolizumab + platinum, durvalumab, nivolumab, and nivolumab + ipilimumab. For pneumonitis, atezolizumab had the lowest rate compared to durvalumab nivolumab, atezolizumab + platinum, pembrolizumab + platinum, and pembrolizumab. For liver irAEs, durvalumab had the lowest rate compared to pembrolizumab, nivolumab, atezolizumab + platinum, pembrolizumab + platinum. Conclusions These findings suggested that, for patients with advanced NSCLC at high risk of irAEs, durvalumab for patients with dermatologic and liver irAEs, pembrolizumab for patients with gastrointestinal irAEs, pembrolizumab + platinum for patients with endocrine irAEs, and atezolizumab for patients with pneumonitis may be the preferred treatment regimens rather than other immune-based therapies.