Cabozantinib for metastatic castration-resistant prostate cancer (mCRPC) following docetaxel: Combined analysis of two phase III trials.
Bibliographic record
Abstract
225 Background: Two phase III trials, COMET-1 and COMET-2, have reported that cabozantinib did not extend overall survival (OS) outcomes compared to prednisone and prednisone plus mitoxantrone respectively, in unselected post-docetaxel patients with mCRPC. We conducted a retrospective analysis of a combined dataset of these trials in an attempt to identify a benefit in subsets of patients based on prognostic risk factors. Methods: Baseline characteristics and survival data were combined for COMET-1 and COMET-2. Prognostic ability of baseline factors on survival was evaluated using Cox proportional hazards regression models, which incorporated the factors in the modern post-docetaxel nomogram and overall bone scan lesion area (BSLA) by computer-assisted analysis. Regression models included trial as a stratification factor. Evaluation of potentially benefited subsets was performed by the use of interaction terms between the factors and cabozantinib. The hazard ratio between cabozantinib and comparator arms was evaluated after adjusting for baseline prognostic factors. All tests were 2-sided and a p-value ≤0.05 was considered statistically significant. Results: A total of 1147 post-docetaxel patients with mCRPC were available (1028 from COMET-1 and 119 from COMET-2). Age, albumin, LDH and BSLA were statistically significant prognostic factors in addition to variables from the Halabi model (site of metastases, pain, docetaxel-free interval, ECOG-PS, hemoglobin, alkaline phosphatase, PSA). There was no consistent interaction effect on survival between cabozantinib vs. comparator arms for any prognostic group. After adjusting for multiple potential prognostic factors, treatment with cabozantinib vs. comparator was associated with an observed hazard ratio of 0.77 (95% CI = 0.65 to 0.92, p = 0.003) for survival. Conclusions: After combining data from both COMET-1 and COMET-2 trials, no differential effect of cabozantinib on survival was observed for any prognostic risk factor. A modest treatment effect of cabozantinib on OS was observed after controlling for multiple potential prognostic factors.
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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 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.007 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".