Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy. Issue 7 (15th July 2019)

• Record Type: Journal Article
• Authors: Tsung, Irene; Dolan, Russell; Lao, Christopher D.; Fecher, Leslie; Riggenbach, Kane; Yeboah‐Korang, Amoah; Fontana, Robert J.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 50:Issue 7(2019)
• Page Start: 800
• Page End: 808
• Publication Date: 2019-07-15
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.15413
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: Background: Pembrolizumab immunotherapy has been associated with hepatotoxicity in 1%‐10% of oncology patients treated in clinical trials. Aim: To describe the incidence, phenotypes and outcomes of liver injury in a large cohort of solid organ tumour patients receiving pembrolizumab Methods: Liver injury was defined by serum alanine aminotransferase, alkaline phosphatase, and/or total bilirubin levels exceeding threshold values. The likelihood of drug‐induced liver injury was adjudicated by expert opinion. Results: Seventy (14.3%) of the 491 pembrolizumab‐treated patients developed liver injury at a median of 62 days (6‐478) and 71.4% had a cholestatic injury profile at onset. The median age, gender and tumour types of liver injury patients were similar to those without, but hepatic metastases (53% vs 21%, P < 0.01) and prior systemic and liver‐directed therapy (71% vs 53%, P < 0.01) were more commonly observed in liver injury patients. During follow‐up, liver injury patients were less likely to experience tumour remission (10% vs 40.4%) and had higher mortality (67.1% vs 33.7%). Only 20 (28.6%) liver injury cases were adjudicated as probable drug‐induced hepatotoxicity; these patients were significantly more likely to present with an hepatocellular/mixed injury pattern (65% vs 12%), to receive corticosteroids (55% vs 12%) and had lower mortality (45% vs 76%) during follow‐up. Conclusions: Oncology patients treated with pembrolizumab who develop liver injury experience poorer outcomes during follow‐up. The low incidence of confirmed drug hepatotoxicity highlights the need for thorough medical evaluation before initiating corticosteroids to optimise patient care.