Hepatic effects assessed by review of safety data in enzalutamide castration-resistant prostate cancer (CRPC) trials.
Bibliographic record
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]
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.023 | 0.034 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.005 |
| Bibliometrics | 0.006 | 0.006 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".