A randomized phase II cross-over study of abiraterone + prednisone (ABI) vs enzalutamide (ENZ) for patients (pts) with metastatic, castration-resistant prostate cancer (mCRPC).
Bibliographic record
Abstract
5002 Background: ABI and ENZ are indicated as 1 st line therapy for mCRPC but have not been directly compared. Optimal sequencing of these agents has not been prospectively evaluated and predictive biomarkers are lacking. Methods: Multicenter, phase 2 study randomizing treatment-naïve mCRPC pts to ABI vs ENZ, with cross over at PSA progression. Primary endpoints: response and time to PSA progression (TTPP, PCWG3 criteria) after 2 nd line therapy. Reported here are secondary endpoints: PSA ≥50% decline (PSA50) from baseline, TTPP with 1 st line therapy, and correlation with deep targeted sequencing of 73 mCRPC genes in circulating tumor DNA (ctDNA). Results: Accrual completed October 2016 with 202 pts randomized (ABI:ENZ = 101:101). Median follow-up 12.8 months. Baseline characteristics were similar between arms: median for age was 75 years (range 49-94), PSA 36.1 (1.7-2817), HGB 130 (89-165), ALK PHOS 105 (31-6600), LDH 207 (77-3098). ECOG PS was 0-1 in 83%, presence of metastases in bone/liver/lung in 83%/6%/10%. With 1 st line therapy for ABI vs ENZ, PSA50 at 12 weeks was 53% vs 73% (P = 0.004), no PSA decline occurred in 21% vs 15% (P = 0.243), and median TTPP was 7.4 vs 8.0 months (HR = 0.88, 95% CI 0.61, 1.27). Baseline ctDNA fraction was >2% in 60% of patients, and associated with worse TTPP (HR 1.80, P=0.005). Baseline pathogenic ctDNA alterations in AR, TP53, RB1, and DNA repair (BRCA2, ATM) genes were associated with a shorter TTPP (univariate analysis: TABLE). On multivariate analysis including clinical factors, TP53 and BRCA2/ATM alterations remained significant (HR = 2.54 (95%CI 1.55-4.19) and HR = 2.68 (1.58-4.54)). Pts with a PSA increase as best response were enriched for alterations in DNA repair (P <0.001), TP53 (P = 0.005), RB1 (P = 0.04), and (in 1 pt) a genomically truncated AR. Conclusions: There was a difference in PSA response for 1 st line ABI vs ENZ, but no difference for TTPP. Baseline pathogenic ctDNA alterations, particularly in TP53 and BRCA2, identify pts with poor outcomes. Clinical trial information: NCT02125357. [Table: see text]
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".