Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic prostate cancer (HSM1PC) patients (pts): Results of S9346 (INT-0162), an international phase III trial.
Bibliographic record
Abstract
4 Background: Castration resistance occurs in the vast majority of HSM1PC pts treated with AD, with a median survival of 2.5 years (y). It is in part an adaptive process with activation of genes resulting in the production of autocrine/paracrine growth factors that contribute to maintaining the viability of PC cells. Replacing androgens before castration resistance is hypothesized to maintain PC androgen-dependence. Preclinically IAD prolonged time to castration resistance and early clinical data indicated feasibility and potential for better quality of life. Methods: HSM1PC pts with performance status (PS) 0-2, PSA ≥ 5 ng/ml were treated with 7 months (m) of goserelin + bicalutamide. Pts achieving PSA ≤4 ng/ml on m 6 and 7 were stratified by prior neoadjuvant AD/finasteride, PS and disease extent (minimal, extensive) and randomized to CAD or IAD. Primary objective: To assess if overall survival (OS) with IAD is noninferior to CAD using a one-sided test with an upper bound hazard ratio=1.20, adjusting for stratification factors. Sample size: 756 pts/arm, type I and II error rates of 0.05 and 0.10. Results: 3,040 pts were accrued by SWOG, CALGB, ECOG, NCIC, and EORTC (5/95- 9/08). After 7 m of CAD, 1535 eligible pts achieved PSA ≤4.0 (median age 70 yrs, 4% PS 2, 48% extensive disease, 12% prior neoadjuvant AD) and were randomized to CAD (759 pts) or IAD (770 pts). Grade 3/4 related adverse events: IAD 30.3%, CAD 32.6%. Median follow-up was 9.2 yrs. Median and 10 yr OS: All eligible pts from study entry: 3.6 yrs, 17%; from randomization CAD: 5.8 yrs, 29%; IAD: 5.1 yrs, 23%, HR (IAD/CAD) = 1.09 (95% CI 0.95, 1.24). No interaction with therapy was significant (p>0.25) except suggestion with disease extent (p=0.08): extensive disease HR=0.96 (95% CI 0.79, 1.15, p=0.64); minimal disease: HR=1.23 (95% CI 1.02, 1.48, p=0.035). PC was cause of death in 56% of CAD and 64% IAD pts. OSby race was not different (p=0.44). Conclusions: In HSM1PC, IAD is not proven to be noninferior to CAD. For extensive disease pts IAD was noninferior; however, IAD was statistically inferior in minimal disease pts suggesting that CAD is the preferred treatment in this group.
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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 | 0.001 |
| 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) | 0.006 | 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".