Adverse events of special interest assessed by review of safety data in enzalutamide castration-resistant prostate cancer (CRPC) trials.
Bibliographic record
Abstract
237 Background: Androgen receptor inhibitor enzalutamide improves survival in patients with metastatic CRPC (mCRPC) and reduces risk of metastasis or death versus placebo in patients with non-metastatic CRPC (nmCRPC). This post hoc analysis evaluated the incidence of adverse events (AEs) of special interest reported with enzalutamide versus placebo in CRPC trials. Methods: Safety data from four Phase 3, placebo-controlled enzalutamide trials in men with CRPC (PROSPER, nmCRPC, NCT02003924; PREVAIL, mCRPC, NCT01212991; AFFIRM, mCRPC, NCT00974311; and 9785-CL-0232, mCRPC, NCT02294461) were assessed for AEs of special interest, including ischemic heart disease (IHD) [defined by narrow Standardised MedDRA Queries “Myocardial Infarction”/“Other Ischemic Heart Disease”], falls, and fractures. Data were reported as overall incidence and adjusted for treatment exposure (per 100 patient-years), and summarized as follows: patients receiving enzalutamide (n = 2799) and placebo (n = 1898) in all four Phase 3 trials. Results: Median treatment duration was 13.73 months with enzalutamide and 4.80 months with placebo in the combined Phase 3 trials. Overall incidence of IHD was higher with enzalutamide versus placebo in the combined Phase 3 trials (Table), remaining higher once adjusted for treatment exposure (2.5 with enzalutamide vs. 2.2 with placebo). Similarly, exposure-adjusted rate of falls and fractures were also higher with enzalutamide versus placebo (Table). Clinical trial information: NCT02003924 (PROSPER); NCT01212991 (PREVAIL); NCT00974311 (AFFIRM); NCT02294461 (9785-CL-0232). Conclusions: In this combined analysis of CRPC trials, incidences of IHD, falls, and fractures were higher with enzalutamide versus placebo in all patients. Efforts to identify patients at high risk for these AEs and reduce their risk, e.g. via exercise and cardiovascular risk reduction, are important in these patients, particularly in elderly men and those with cardiovascular comorbidities.[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 | 0.034 | 0.047 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.007 |
| Bibliometrics | 0.004 | 0.005 |
| 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".