Overall survival with darolutamide vs placebo in combination with androgen-deprivation therapy (ADT) and docetaxel: A sensitivity analysis from ARASENS accounting for subsequent therapy.
Bibliographic record
Abstract
166 Background: Darolutamide (DARO) + ADT + docetaxel (DOC) is approved for metastatic hormone-sensitive prostate cancer (mHSPC) based on the phase 3 ARASENS study (NCT02799602). To address the impact of informative intercurrent events (eg, use of subsequent therapy) in censored patients (pts), as defined by the European Medicines Agency, we performed a post hoc sensitivity analysis of OS. Methods: Pts with mHSPC were randomized 1:1 to oral DARO 600 mg twice daily or placebo (PBO) + ADT + DOC. The primary endpoint was OS using a log-rank test, with HR (95% CI) calculated by Cox model, stratified by extent of disease (EoD; nonregional lymph node vs bone ± lymph node vs visceral ± lymph node/bone metastases) and alkaline phosphatase (< vs ≥ upper limit of normal). Pts with no documented death were censored at last known alive or data cut-off date, whichever was earlier. The post hoc sensitivity analysis counted initiation of subsequent systemic antineoplastic therapy as an event in censored pts still alive at end of follow-up. In addition planned sensitivity analyses used an unstratified log-rank test/Cox model, a log-rank test/Cox model with stratification factors from electronic case report forms, and a log-rank test/Cox model with EoD stratification factors from central imaging review. Results: In the primary analysis DARO + ADT + DOC significantly improved OS ( P<0.0001; Table), despite a high percentage of pts who entered follow-up in the PBO group receiving subsequent life-prolonging systemic therapies (374/495, 76%). Time to first subsequent systemic antineoplastic therapy (a key secondary endpoint) was significantly longer with DARO + ADT + DOC vs PBO + ADT + DOC (HR 0.39, 95% CI 0.33–0.46, P<0.001). Findings from the post hoc sensitivity analysis counting initiation of subsequent systemic antineoplastic therapy as an event in censored pts (pts with events: DARO 300/651, 46.1%; PBO 476/654, 72.8%) and the planned sensitivity analyses were consistent and supported the primary OS analysis (Table). Treatment-emergent adverse events (TEAEs) were similar between groups. TEAEs led to DARO/PBO discontinuation in 13.5%/10.6% of pts. Conclusions: The results of the post hoc and planned sensitivity analyses were consistent with and supportive of the ARASENS primary OS analysis. These data reinforce DARO + ADT + DOC as an effective and well tolerated new standard of care for early treatment intensification in pts with mHSPC. Clinical trial information: NCT02799602 . [Table: see text]
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.024 | 0.013 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.019 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 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".