Results from a phase 3, randomized, double-blind, multicenter, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy (ELM-PC 5 trial).
Bibliographic record
Abstract
7^ Background: Orteronel is an investigational, non-steroidal selective inhibitor of 17,20-lyase; a key enzyme in the production of steroidal hormones. Methods: Eligible men with metastatic castration-resistant prostate cancer (mCRPC) had progressive disease (PD; radiographic or prostate-specific antigen), castrate levels of testosterone, and had received more than or equal to 360 mg/m 2 docetaxel within the prior 6 months. Prior orteronel, abiraterone, or ketoconazole was not permitted. Patients were randomized 2:1 to continuous 28-day cycles of oral orteronel 400 mg BID + prednisone 5 mg BID, or placebo + prednisone without regard to food. Primary endpoint: overall survival (OS); other key endpoints: radiographical progression-free survival (rPFS), 50% or more PSA decrease at 12 weeks, pain response at 12 weeks and safety (NCT01193257). Results: One thousand ninety nine patients were randomized.The study was terminated for failing to meet its primary endpoint: median overall survival (OS) was 17.0 months (95% CI 15.2, 19.9) in patients receiving orteronel versus 15.2 months (95% CI 13.5, 16.9) in those receiving placebo (HR: 0.886 [95% CI: 0.739, 1.062]; P=0.1898). Substantial regional differences were seen in OS benefit: median OS (orteronel vs. placebo) was 20.9 vs. 16.9 mo (HR: 0.889) in North America (n=112), 18.3 vs. 17.8 mo (HR: 1.048) in Europe (n=590), and 15.3 vs 10.1 mo (HR: 0.709) in the rest of the world (n=397). In the overall population, rPFS was significantly improved in the orteronel arm, with a median of 8.3 months vs. 5.7 months in the placebo arm (HR: 0.76 [95% CI: 0.653, 0.885]; P=0.00038). Drug-related adverse events (AEs; any grade) included (orteronel/placebo) nausea (30/16%), vomiting (23/8%), fatigue (17/11%), and diarrhea (16/9%); grade 3 or higher drug-related AEs included increased lipase (12/less than 1%), increased amylase (8/less than 1%), and fatigue (3/3%). Additional sub-analyses looking at potential factors that affected OS will also be reported. Conclusions: Whileorteronel + prednisone did not show a statistically significant overall OS improvement versus placebo + prednisone, rPFS findings and striking regional OS differences suggest that orteronel has clinically meaningful activity. Clinical trial information: NCT01193257.
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 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 | 0.007 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.001 |
| 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".