Increased risk of liver toxicity secondary to nivolumab therapy in the treatment of cancer.
e14559 Background: Nivolumab, a humanized immunotherapy targeting PD-1, is approved for the treatment of a number of solid and liquid cancers and is associated with liver toxicity. This meta-analysis was conducted to determine the overall risk of hepatotoxicity with nivolumab therapy in cancer patients. Methods: An analysis from all phase I, II, and II clinical trials up to December 2016 examining the role of nivolumab in a variety of cancers was conducted. Eligible trials included those in which patients received nivolumab. Data on all-grade and high-grade (grade 3 and 4) elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were extracted from the safety profiles of each clinical trial. Incidence and relative risk (RR) were calculated using random - or fixed - effect models with 95% confidence intervals. Results: The data from 27 eligible trials were included for analysis. A total of 5,287 patients were evaluated (Nivolumab: n = 3515, Control: n = 1772). The incidences of all-grade and high-grade elevations in AST were 5.4% (95% CI: 3.2% - 9.1%) and 1.60% (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 1.5% (95% CI: 0.9% - 3.1%), respectively. Elevations of both laboratory markers were significantly increased when compared to control (P < 0.001). Nivolumab increased the RR of AST/ALT elevations; RR of all-grade AST elevations was 1.58 (95% CI: 1.1 - 2.2), all-grade ALT elevations was 1.62 (95% CI: 1.2 - 2.3). Subgroup analysis of all-grade AST elevations revealed melanoma patients exhibited a significantly higher rate compared to other solid tumors with an incidence of 8.7% (95% CI: 4.3 - 18.2%). All-grade ALT elevations in melanoma patients revealed the same incidence rate. Of note, renal cell carcinoma patients exhibited a particularly low incidence of all-grade transaminitis with AST 1.6% (95% CI: 0.6 - 11.1%) and ALT 1.8% (95% CI: 0.6 - 14.6%). Conclusions: Nivolumab is associated with significantly increased risk of all-grade and high-grade elevations in AST and ALT. Therapy should include careful monitoring of hepatotoxicity.