Comparative risk of serious and fatal treatment-related adverse events caused by 19 immune checkpoint inhibitors used in cancer treatment: a network meta-analysis.

ABSTRACT: Background:This network meta-analysis assessed the comparative risk of grade 3-5 and grade 5 treatment-related adverse events (TRAEs) for immune checkpoint inhibitors (ICIs), either alone or in combination with other modalities, for cancer treatment. Methods:PubMed, Embase, Cochrane Library, Web of Science, and recent predominant oncology congresses were searched for relevant phase?II and phase?III randomized controlled trials (RCTs). As outcomes, grade 3-5, and grade 5 TRAE outcomes were reported as odds ratios and 95% confidence intervals. Results:In 67 RCTs involving 36,422 patients and 19 ICIs, the incidence of grade 3-5 and grade 5 TRAEs was 17.9% and 0.8% with ICI monotherapy and 46.3% and 1.4%, respectively, with combinatorial therapy. Pneumonitis was the most common cause of grade 5 TRAEs following either monotherapy (16.3%) or combinatorial therapy (11.4%). Regarding grade 3-5 TRAEs, atezolizumab?+?chemotherapy (CT) and antiangiogenic therapy (AT) (atezolizumab?+?CAT), pembrolizumab?+?CT, ipilimumab?+?CT, and atezolizumab?+?CT were more toxic than any ICI monotherapy, pembrolizumab or nivolumab?+?radiotherapy (RT), and ICIs dual therapy (durvalumab?+?tremelimumab and nivolumab?+?ipilimumab). Tremelimumab, ipilimumab, durvalumab, and pembrolizumab were, however, associated with higher grade 5 TRAEs than combinatorial treatments. Atezolizumab?+?CAT was the most toxic and nivolumab?+?RT was the least toxic of combinatorial treatments; among monotherapies, tremelimumab and avelumab were the most and least toxic, respectively. The toxicity ranking changed with type of grade 3-5 TRAEs. Conclusions:Compared with combinatorial therapy, ICI monotherapy caused lower grade 3-5 TRAEs, but some monotherapies resulted in a higher incidence of fatal TRAEs. Atezolizumab?+?CAT and nivolumab?+?RT were the most and least toxic of combinatorial treatments, respectively, and tremelimumab and avelumab were the most and least toxic of the monotherapies, respectively.

SUBMITTER: Liu T 

PROVIDER: S-EPMC7394035 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature