Hepatic effects assessed by review of safety data in enzalutamide castration-resistant prostate cancer (CRPC) trials.

Abstract

199 Background: Androgen receptor inhibitor enzalutamide (ENZA) improves survival in patients with metastatic CRPC. As the liver is the main route of ENZA elimination, this post hoc analysis evaluated the hepatic effects of ENZA versus comparators in controlled CRPC trials. Methods: Safety data from two large Phase 3, placebo (PBO)- (PREVAIL, NCT0121299; AFFIRM, NCT00974311) and two smaller Phase 2, bicalutamide (BIC)-controlled (STRIVE, NCT01664923; TERRAIN, NCT01288911) ENZA trials in men with CRPC were assessed for hepatic impairment-related adverse events (AEs) using the following standardized narrow MedDRA queries V19.1: hepatic failure, fibrosis and cirrhosis, and other liver damage-related conditions; hepatitis, non-infectious; and liver-related investigation, signs, and symptoms. Liver-related laboratory test results were also evaluated. Data were summarized as follows: patients receiving ENZA in Phase 3 trials (n = 1671); patients receiving ENZA in Phase 2 trials (n = 380); patients receiving PBO (n = 1243); patients receiving BIC (n = 387); and combined ENZA-treated patients (n = 2051). Results: Percentages of hepatic impairment-related AEs ranged between 2.9% and 4.5% with ENZA, and were 2.7% with PBO and 5.4% with BIC (Table). The most common hepatic impairment-related AEs were increased aspartate (AST) and alanine aminotransferase (ALT; Table). Within each trial, the incidences of grade ≥3 AEs were similar, and dose reductions or discontinuations due to hepatic impairment-related AEs were low (Table). When adjusted for treatment exposure, AEs per 100 patient-years were lower with ENZA versus either PBO or BIC (Table). Conclusions: This combined analysis of CRPC trials demonstrates no hepatic safety signal with ENZA and thus routine liver tests are not required. Clinical trial information: NCT0121299; NCT00974311; NCT01664923; NCT01288911. [Table: see text]