Final analysis of COMET-1: Cabozantinib (Cabo) versus prednisone (Pred) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) previously treated with docetaxel (D) and abiraterone (A) and/or enzalutamide (E).
Bibliographic record
Abstract
139 Background: Cabo inhibits tyrosine kinases including MET and VEGFRs. In a phase 2 study in mCRPC pts, Cabo was associated with improvements in bone scans, pain, measurable disease, and circulating tumor cells. COMET-1 compared the effects of Cabo versus Pred on overall survival (OS) in men with progressive mCRPC and prior D and A and/or E. Methods: In this randomized, double-blind, controlled phase 3 study (NCT01605227), pts with mCRPC and prior D and A and/or E were randomized 2:1 to receive Cabo (60 mg qd) or Pred (5 mg bid). Pts were stratified by prior treatment with cabazitaxel, ECOG status, and presence of moderate to severe pain. The primary endpoint was OS. The study was designed to observe 578 deaths to provide 90% power to detect a hazard ratio (HR) of 0.75. A secondary endpoint was bone scan response at Week 12 (BSR) determined by central independent radiology committee, defined as a ≥30% decrease in the bone scan lesion area compared to baseline. Exploratory endpoints include PFS and OS subgroup analyses. Results: 1,028 pts were randomized between Jul 2012 and Nov 2013. In the final analysis after 614 deaths, the estimated median OS was 11.0 months for Cabo vs 9.8 months for Pred (HR 0.90; 95% CI: 0.0.76-1.06; P = 0.212). The secondary endpoint of BSR was 41% for Cabo vs 3% for Pred (P <0.001). Median PFS per investigator was 5.5 months for Cabo vs 2.8 months for Pred (HR 0.50; P <0.001). For 191 pts with visceral disease median OS was 7.1 months for Cabo vs 4.8 months for Pred (HR 0.65; P = 0.0215). 371 (54.4%) and 233 (67.3%) pts received salvage therapy in the Cabo and Pred arms, respectively. Subsequent cabazitaxel and/or D was reported in 107 (15.7%) and 104 (30.1%) Cabo and Pred pts, respectively. Serious adverse events of pulmonary embolism, nausea, dehydration and fatigue were more frequent with Cabo. Conclusions: Compared to prednisone, Cabo improved BSR and PFS but did not significantly increase OS. The improvement in OS was greatest in the subset of patients with visceral metastases. The activity and safety profile of Cabo was similar to that observed in phase 2 studies in mCRPC. Clinical trial information: NCT01605227.
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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".