Severe immune-related adverse events of immune checkpoint inhibitors for advanced non-small cell lung cancer: a network meta-analysis of randomized clinical trials.

OBJECTIVE:A complete toxicity profile, toxicity profile, and safety ranking of immune checkpoint inhibitors (ICIs) for treatment of advanced non-small cell lung cancer (NSCLC) will be provided in this network meta-analysis. METHODS:We searched 14 randomized clinical trials (RCTs) including 9572 NSCLC patients by PubMed, EMBASE, Cochrane, and ClinicalTrials.gov. Randomized pairwise and network meta-analyses were used to compare the incidence of severe immune-related adverse events (irAEs) across different ICIs-based treatments using risk ratios (RRs) and 95% confidence intervals (CI). RESULTS:For severe dermatologic irAEs, the corresponding ranking of incidences of the nine groups from high to low was: nivolumab + ipilimumab + platinum (79.1%), pembrolizumab (75.2%), nivolumab + ipilimumab (72.9%), camrelizumab + platinum (64.9%), atezolizumab + platinum (47.4%), nivolumab (44.2%), durvalumab (40.5%), pembrolizumab + platinum (15.5%), platinum-based chemotherapy (10.3%). For severe colitis, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab + platinum (72.4%), nivolumab (63.1%), atezolizumab + platinum (56.9%), durvalumab (56.6%), pembrolizumab (54.9%), pembrolizumab + platinum (38.6%), platinum-based chemotherapy (7.4%). For severe endocrine irAEs, the corresponding ranking of incidences of the nine groups from high to low was: durvalumab (74.3%), atezolizumab + platinum (54.5%), nivolumab + ipilimumab (54.0%), camrelizumab + platinum (51.7%), nivolumab + ipilimumab + platinum (51.6%), pembrolizumab + platinum (49.8%), pembrolizumab (49.2%), nivolumab (46.3%), platinum-based chemotherapy (18.6%). For severe pneumonitis, the corresponding ranking of incidences of the nine groups from high to low was: nivolumab (84.3%), pembrolizumab (84.1%), durvalumab (66.1%), camrelizumab + platinum (61.4%), atezolizumab + platinum (50%), pembrolizumab + platinum (43.4%), platinum-based chemotherapy (16.2%), atezolizumab (6.2%). For severe hepatitis, the corresponding ranking of incidences of the eight groups from high to low was: pembrolizumab (68.8%), nivolumab + ipilimumab + platinum (65%), pembrolizumab + platinum (64.6%), durvalumab (57.9%), nivolumab (47.1%), atezolizumab + platinum (43.4%), camrelizumab + platinum (42%), platinum-based chemotherapy (11.2%). CONCLUSIONS:In addition to platinum-based chemotherapy, pembrolizumab + platinum for severe dermatologic irAEs and colitis, nivolumab for severe endocrine irAEs, atezolizumab for severe pneumonitis, camrelizumab + platinum for severe hepatitis may be associated with lower rates of irAEs than other immune-based regimens.