Final overall survival (OS) in PROpel: Abiraterone (abi) and olaparib (ola) versus abiraterone and placebo (pbo) as first-line (1L) therapy for metastatic castration-resistant prostate cancer (mCRPC).
Bibliographic record
Abstract
LBA16 Background: PROpel (NCT03732820) met its primary endpoint showing significant investigator-assessed radiographic progression-free survival (rPFS) benefit for patients with mCRPC treated with abi + ola vs abi + pbo in the 1L setting (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81, P< 0.001, data cut-off: 7/30/2021). Sensitivity analysis by blinded independent central review was consistent. A trend toward OS benefit with abi + ola was observed at the time of the primary rPFS analysis (28.6% maturity, HR 0.86, 95% CI 0.66–1.12) and a subsequent interim analysis (40.1% maturity, HR 0.83, 95% CI 0.66–1.03). We report OS and safety from the pre-planned final analysis (data cut-off: 10/12/2022). Methods: PROpel is a randomized, double-blind phase 3 trial of 1L therapy for patients with mCRPC eligible for abiraterone. Patients were prospectively assessed for homologous recombination repair mutation (HRRm) status using tumor tissue (FoundationOne CDx) and/or circulating tumor DNA (ctDNA; FoundationOne Liquid CDx) tests after randomization 1:1 to ola (300 mg twice daily [bid]) or pbo, and abi (1000 mg once daily) plus prednisone/prednisolone (5 mg bid). Treatment continued until radiographic disease progression, unacceptable toxicity or withdrawal of consent. OS was a key secondary endpoint (2-sided boundary for significance 0.0377). Aggregate results from tumor tissue and ctDNA tests were used to assign patients to HRRm/BRCAm subgroups. Results: Patient (n = 796) characteristics (including prior docetaxel, site of metastasis, symptom score and HRRm status) were generally balanced. There was a consistent trend toward OS benefit in the intention-to-treat (ITT) population with abi + ola vs abi + pbo (maturity 47.9%, HR 0.81, 95% CI 0.67–1.00, P= 0.0544), with median OS 42.1 months (m) vs 34.7 m, respectively. OS medians and HRs for HRRm, non-HRRm, BRCAm and non-BRCAm subgroups all favored abi + ola vs abi + pbo. In the abi + ola arm the most common Grade ≥3 adverse event was anemia (16.1%). Conclusions: At the prespecified final analysis in PROpel, abi + ola prolonged OS by > 7 m vs standard-of-care abiraterone (abi + pbo) in the ITT population. The median OS of > 42 m is the longest median reported to date in a phase 3 trial in 1L mCRPC. Consistent with rPFS results, a trend toward OS benefit was observed in HRRm, non-HRRm, BRCAm and non-BRCAm subgroups with greatest benefit in the BRCAm subgroup. No new long-term safety issues were identified. These results support the use of abi + ola in 1L mCRPC. Clinical trial information: NCT03732820 . [Table: see text]
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".