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Post-progression survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who received darolutamide or placebo: Post hoc analysis of ARASENS.

2024· article· en· W4399394859 on OpenAlexaff
Marc‐Oliver Grimm, Matthew R. Smith, Maha Hussain, Fred Saad, Karim Fizazi, Natasha Littleton, Noman Paracha, Shankar Srinivasan, Frank Verholen, Bertrand Tombal

Bibliographic record

VenueJournal of Clinical Oncology · 2024
Typearticle
Languageen
FieldMedicine
TopicProstate Cancer Treatment and Research
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsMedicinePost-hoc analysisOncologyProstate cancerInternal medicinePlaceboCancerPathology

Abstract

fetched live from OpenAlex

5083 Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor pathway inhibitor (ARPI). In ARASENS (NCT02799602), the addition of DARO to androgen-deprivation therapy (ADT) and docetaxel (DOC) significantly reduced the risk of death by 32.5% in patients (pts) with mHSPC, despite most placebo (PBO) pts (75.6%) receiving subsequent therapy. DARO also delayed time to progression to metastatic castration-resistant prostate cancer (mCRPC; median, not reached vs 19.1 months for PBO), resulting in a longer time in mHSPC, which is associated with improved quality of life vs mCRPC. We report post-progression subsequent anticancer therapies and related survival from ARASENS. Methods: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or PBO in addition to ADT + DOC. After treatment discontinuation, pts entered active and long-term survival follow-up periods during which assessments included subsequent therapies and survival outcomes. Post-progression survival was defined as time from first subsequent therapy to death using Kaplan-Meier estimates. Results: Of 1305 treated pts (DARO n=651; PBO n=654), 315 receiving DARO and 495 receiving PBO entered follow-up. Of these, 57% (n=179) and 76% (n=374), respectively, received subsequent therapy; abiraterone and enzalutamide were the most frequent first subsequent therapy (Table). In the DARO arm, 90% of first subsequent therapies were ARPI or chemotherapy. Minimal difference was observed in post-progression survival between subsequent therapies, suggesting subsequent therapy with another ARPI does not provide further survival benefit vs non-ARPI options (mainly chemotherapy). In contrast, in the PBO arm where the majority (78%) received first subsequent therapy with an ARPI, a survival benefit was observed vs non-ARPI subsequent therapies (median, 23.0 vs 13.5 months). Conclusions: DARO+ADT+DOC increased overall survival vs PBO+ADT+DOC and also delayed time to progression to mCRPC. DARO pts had similar survival with all post-progression therapies. Pts receiving PBO+ADT+DOC quickly progressed to mCRPC and treatment with an ARPI in ARPI-naïve pts improved survival. 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 imitation

Not 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.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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.

Opus teacher head0.079
GPT teacher head0.475
Teacher spread0.396 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

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