Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients.

PURPOSE: The aim of this study was to evaluate the risk of immune-related adverse events (irAEs) among cancer patients receiving nivolumab-plus-ipilimumab therapy and nivolumab monotherapy. PATIENTS AND METHODS: PubMed and Web of Science were searched for related studies from inception to June 2018. Eligible studies included randomized controlled trials comparing nivolumab-plus-ipilimumab with nivolumab alone in cancer patients reporting on all-grade (grade 1-4) and high-grade (grade 3/4) irAEs. Paired reviewers selected studies for inclusion and extracted data. The odds risk and 95% CI were calculated. RESULTS: A total of 2,946 patients from four studies were included in the meta-analysis. The underlying malignancies included lung cancer (two trials) and melanoma (two trials). Compared with nivolumab monotherapy, the nivolumab-plus-ipilimumab therapy was associated with a significantly higher risk of all- and high-grade irAEs such as pruritus, rash, diarrhea, colitis, alanine aminotransferase elevation, and pneumonitis. CONCLUSION: The combination therapy of nivolumab and ipilimumab increased the incidence of irAEs in patients with advanced cancer.