Novel androgen receptor inhibitors in nonmetastatic castration-resistant prostate cancer: A network meta-analysis.
Bibliographic record
Abstract
131 Background: Novel non-steroidal anti-androgens (NSAAs) including enzalutamide, apalutamide, and darolutamide with androgen deprivation therapy (ADT) have proven efficacy in men with high-risk non-metastatic castrate resistant prostate cancer (nmCRPC). However, in the absence of direct comparative trials, there is little evidence to guide therapeutic choice. Our objective was to perform a network meta-analysis to compare agents and perform a class-level meta-analysis of NSAAs with androgen deprivation therapy (ADT) versus ADT-alone. Methods: We performed a systematic review of phase III parallel-group RCTs in men ≥18 years of age with nmCRPC using EMBASE and MEDLINE, indexed as of March 8, 2019. Our primary outcome was metastasis free survival (MFS). Secondary outcomes included OS, PSA progression free survival (PFS), and rates of grade 3-4 adverse events (AEs). Three RCTs were identified. We performed a random effects meta-analysis of NSAA versus ADT-alone using the inverse variance technique for meta-analysis for efficacy outcomes and the Mantel-Haenszel method for meta-analysis of dichotomous data for AEs. We then performed a network meta-analysis to compare outcomes between NSAAs using fixed-effect models in a Bayesian framework. We estimated the relative ranking of the different treatments for each outcome. Results: Pooled MFS, PSA-PFS, and OS were significantly greater with NSAA versus placebo (HR:0.32,95%CI:0.25-0.41, HR:0.08,95%CI:0.05-0.13, and HR:0.74,95%CI:0.61-0.90, respectively). Apalutamide and enzalutamide had a 56% and 44% likelihood of maximizing MFS, respectively. There was a 44%, 41%, and 15% likelihood that apalutamide, darolutamide and enzalutamide offered the greatest OS benefit, respectively. There was a 61% chance that darolutamide was preferred with respect to AEs. Conclusions: NSAAs improve survival outcomes in patients with high-risk nmCRPC. Apalutamide and enzalutamide may offer improved oncological outcomes. Darolutamide may result in fewer adverse events. These differences, if confirmed, would be meaningful to patients and practitioners when selecting treatment.
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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 | 0.021 | 0.028 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.058 |
| Bibliometrics | 0.006 | 0.006 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
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".