Overall survival with darolutamide versus placebo in combination with androgen-deprivation therapy and docetaxel for metastatic hormone-sensitive prostate cancer in the phase 3 ARASENS trial.
Bibliographic record
Abstract
13 Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor that demonstrated improved overall survival (OS) and metastasis-free survival vs placebo (PBO) and a low incidence of treatment-emergent adverse events (TEAEs) in patients (pts) with nonmetastatic castration-resistant prostate cancer (CRPC). We investigated whether DARO in combination with standard androgen-deprivation therapy (ADT) + docetaxel would increase OS in pts with metastatic hormone-sensitive prostate cancer (mHSPC) in the ARASENS study (NCT02799602). Methods: This international, double-blind, phase 3 study enrolled pts with mHSPC and ECOG PS 0/1 who were randomized 1:1 to DARO 600 mg twice daily or matching PBO in addition to ADT + docetaxel. Randomization was stratified by extent of disease according to TNM (M1a vs M1b vs M1c) and alkaline phosphatase levels ( < vs ≥ upper limit of normal). The primary endpoint was OS. Secondary efficacy endpoints included time to CRPC, time to pain progression, time to first symptomatic skeletal event (SSE), and time to initiation of subsequent systemic antineoplastic therapies. Safety was also assessed. Results: From Nov 2016 to June 2018, 1306 pts were randomized, 651 to DARO and 655 to PBO, in combination with ADT + docetaxel. Median age was 67 y in both arms. At the primary data cutoff (Oct 25, 2021), DARO significantly decreased the risk of death by 32.5% vs PBO (HR 0.675, 95% CI 0.568–0.801; P < 0.0001). The significant improvement in OS was observed even though substantially more pts received subsequent life-prolonging systemic antineoplastic therapy in the PBO arm (75.6%) vs the DARO arm (56.8%). The significant OS benefit was consistent across prespecified subgroups. In addition, DARO significantly delayed time to CRPC versus PBO (HR 0.357, 95% CI 0.302–0.421; P < 0.0001). Time to pain progression was also significantly longer with DARO vs PBO (HR, 0.792, 95% CI 0.660–0.950; P= 0.0058), as were time to first SSE and time to initiation of subsequent systemic antineoplastic therapy. TEAEs were similar between treatment arms, and the incidences of the most common TEAEs (≥10%) were highest during the overlapping docetaxel treatment period for both arms, with grade 3/4 TEAEs of 66.1% for DARO and 63.5%for PBO, mainly due to neutropenia (33.7% vs 34.2%, respectively). TEAEs led to treatment discontinuation in 13.5% of pts in the DARO arm and 10.6% of pts in the PBO arm. Conclusions: In pts with mHSPC, early treatment combining DARO with ADT + docetaxel significantly increased OS and improved key secondary endpoints vs ADT + docetaxel alone. The incidence of TEAEs was similar in the two treatment arms. Clinical trial information: NCT02799602.
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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 | 0.002 |
| 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) | 0.004 | 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".