Cabazitaxel Versus Abiraterone or Enzalutamide for Poor-prognosis Metastatic Castration-resistant Prostate Cancer After Docetaxel: A Phase 2 Trial with a Circulating Tumor DNA Analysis
Bibliographic record
Abstract
BACKGROUND AND OBJECTIVE: Whether cabazitaxel or an androgen receptor pathway inhibitor (ARPI) is the optimal treatment option for poor-prognosis metastatic castration-resistant prostate cancer (mCRPC), progressing on docetaxel, remains unclear. There are limited prospective data supporting a preference for one of these treatments and few candidate biomarkers to inform individual patient management. This study aims to compare the clinical efficacy of cabazitaxel versus ARPIs in patients with poor-prognosis mCRPC who have progressed on docetaxel, and to evaluate the prognostic and predictive utility of circulating tumor DNA (ctDNA) in this treatment-refractory population. METHODS: every 3 wk plus prednisone daily). The primary endpoint was the clinical benefit rate (CBR) at 12 wk. The secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and PSA50 response. Genomic analyses on plasma utilized targeted cell-free DNA sequencing at baseline, 12 wk, and progression. KEY FINDINGS AND LIMITATIONS: In total, 106 patients were randomized. The CBR at 12 wk was 62.3% (66/106), with no difference between treatments (p = 0.54). Between groups, rPFS and OS (median follow-up of 30.9 mo) were not different. PSA50 was higher in the ARPI arm (47.2%) than in the cabazitaxel arm (26.9%; p = 0.04). Prior ARPI exposure (in 37.7%) predicted inferior outcomes on ARPIs but not on cabazitaxel. Adverse events of grade ≥3 were more frequent with cabazitaxel (65.4% vs 30.2%). A high baseline ctDNA fraction correlated with reduced rPFS and OS; plasma AR copy number status was not associated with outcomes, but PTEN alterations were linked with shorter OS (hazard ratio: 1.9, multivariable p = 0.02). CONCLUSIONS AND CLINICAL IMPLICATIONS: No significant differences in CBR or time-to-event endpoints were observed between cabazitaxel and ARPIs. However, prior ARPI exposure, a higher baseline ctDNA fraction, and PTEN alterations were strongly prognostic.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".