A Deep Prostate-specific Antigen Response to Darolutamide plus Androgen Deprivation Therapy Is Associated with Better Clinical Outcomes in the Phase 3 ARANOTE Trial in Patients with Metastatic Hormone-sensitive Prostate Cancer
Bibliographic record
Abstract
BACKGROUND AND OBJECTIVE: Darolutamide plus androgen deprivation therapy (ADT) significantly improved radiological progression-free survival (rPFS) versus ADT in ARANOTE (NCT04736199). Here we report prostate-specific antigen (PSA) responses and their correlation with clinical outcomes. METHODS: Patients with metastatic hormone-sensitive prostate cancer were randomized to darolutamide 600 mg twice daily or placebo plus ADT. The proportion of patients achieving undetectable PSA (<0.2 ng/ml) and ultra-low PSA (<0.02 ng/ml) were determined overall and by baseline PSA category. A post hoc analysis was conducted to identify any correlation of rPFS, overall survival (OS), time to metastatic castration-resistant prostate cancer (mCRPC), and time to PSA progression with PSA responses and baseline PSA using an unstratified Cox regression model. KEY FINDINGS AND LIMITATIONS: The rate of achievement of PSA <0.2 ng/ml and of PSA <0.02 ng/ml at any time was threefold greater (63% vs 18%) and fivefold greater (43% vs 7.8%), respectively, in the darolutamide arm versus the placebo arm, with a consistent effect across baseline PSA subgroups. Depending on baseline PSA, up to 88% of patients treated with darolutamide achieved undetectable PSA and up to 69% achieved ultra-low PSA. Achievement of PSA <0.2 ng/ml versus ≥0.2 ng/ml was associated with much better rPFS, OS, time to mCRPC, and PSA progression, with hazard ratios of 0.19 (95% confidence interval [CI] 0.13-0.27), 0.14 (95% CI 0.09-0.21), 0.16 (95% CI 0.12-0.23), and 0.08 (95% CI 0.05-0.12), respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Darolutamide resulted in deep and durable PSA responses, regardless of baseline PSA. A deep PSA response was associated with better clinical outcomes, and patients reaching ultra-low PSA had the greatest clinical benefits from darolutamide.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".