Risk of Liver Toxicity with Nivolumab Immunotherapy in Cancer Patients

Background: Nivolumab is approved for the treatment of many cancers. This meta-analysis was conducted to determine the risk of hepatotoxicity with nivolumab therapy. Methods: An analysis from all phase I-III clinical trials up to December 2016 examining nivolumab was conducted. Data on elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were extracted from the safety profiles of each trial. Incidence and relative risk (RR) were calculated using random-or fixed-effects models with 95% confidence intervals (CIs). Results: The incidences of all-grade and high-grade elevations in AST were 5.4% (95% CI 3.2-9.1) and 1.6% (95% CI 0.9-3.0), respectively. The incidences of all-grade and high-grade elevations in ALT were 4.9% (95% CI 2.9-8.2) and 1.7% (95% CI 0.9-3.1), respectively. Elevations of both laboratory markers were significantly increased when compared to control (p < 0.001). Nivolumab significantly increased the RR of AST/ALT elevations; RRs were 1.58 (95% CI 1.1-2.2) for all-grade AST elevation, and 1.62 (95% CI 1.2-2.3) for all-grade ALT elevation. Subgroup analysis of all-grade AST or ALT elevation revealed a signi-ficant variation among tumor types (p < 0.001) and with combination with ipilimumab (p < 0.001). Conclusions: Nivolumab is associated with significantly increased risk of liver toxicity.