Final analysis of COMET-2: Cabozantinib (Cabo) versus mitoxantrone/prednisone (MP) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) with moderate to severe pain who were previously treated with docetaxel (D) and abiraterone (A) and/or enzalutamide (E).
Bibliographic record
Abstract
141 Background: Cabo inhibits tyrosine kinases including MET and VEGFRs. In a phase 2 study in mCRPC pts, Cabo was associated with improvements in pain, bone scans, measurable disease, and circulating tumor cells. COMET-2 compared the effects of Cabo versus MP on pain palliation in men with progressive mCRPC. Methods: In this double-blind, controlled phase 3 study (NCT01522443), pts with moderate to severe pain and disease progression following D, and A and/or E were randomized 1:1 to receive Cabo (60 mg qd) or MP (12 mg/m2 q3wk and 5 mg bid, resp). All pts were required to have a 7-day average of 4+ pain per Brief Pain Inventory (BPI) item 3 while on an optimized narcotics regimen at baseline. Randomization was stratified by prior cabazitaxel and ECOG performance status. The primary endpoint was pain response (≥30% reduction in BPI item 3) at week 6, confirmed at week 12, without increase in narcotics. The original sample size (N = 246) was selected to achieve at least 90% power to detect an increase in pain response with Cabo (25%) vs. MP (8%) using a two-sided α = 0.05 chi-squared test. The secondary efficacy endpoints were bone scan response (BSR) and overall survival (OS). Results: 119 pts were randomized between March 2012 and July 2014. Randomization was concluded prior to reaching the planned sample size because the companion study COMET-1 did not show a significant OS benefit compared to P in a similar population. Pain response rates were 15% for Cabo vs 17% for MP (P = 0.773). BSR rates were 31% for Cabo vs 5.2% for MP. Median OS was 9 months for Cabo vs 7.9 months for MP. Most frequent G3/4 AEs in the Cabo arm were anemia (22% vs 26% MP), hypertension (22% vs 0% MP), fatigue (18% vs 8.8% MP), and AST increased (10% vs 1.8% MP), with fewer pts discontinuing study treatment for AEs in the Cabo arm (16% vs 26% MP). Conclusions: The primary endpoint of improving pain response was not achieved in this heavily pretreated population. The key secondary endpoints of BSR and OS showed trends favoring the Cabo arm, and no new safety signals were observed at the dose of 60 mg. Clinical trial information: NCT01522443.
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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 | 0.013 | 0.010 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.008 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.010 | 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".