Age as a predictive and prognostic factor for targeted therapy treatment in metastatic chemorefractory colorectal cancer (CRC): An analysis of NCIC CTG CO.17 and CO.20.
Bibliographic record
Abstract
3555 Background: There is minimal data on the efficacy and improvement of quality of life (QoL) of these targeted therapies, like cetuximab, in elderly CRC patients (≥70yo). We analyzed outcomes from two randomized phase III clinical trials from the Canadian Clinical Trials Group, CO.17 and CO.20. Methods: CO.17 and CO.20 were retrospectively analyzed. CO.17 compared cetuximab (CETUX) with best supportive care (BSC), CO.20 compared CETUX + brivanib (BRIV) with CETUX + placebo. Key eligibility criteria were similar between each trial. Patients were dichotomized by age (≥70yo/ < 70yo) for comparisons. Outcomes included overall survival (OS), progression free survival (PFS), adverse events (AEs), and QoL deterioration. In CO.17, only patients with wild type K-RAS were included in analysis. Multivariate analysis with Cox regression controlled for additional variables. Results: 980 patients were included in this analysis. 257 (26.2%) were ≥70yo at the time of enrollment. In CO.17, OS and PFS were similar between young and elderly patients treated with CETUX (OS 9.7m vs 8.0m, p = 0.45; HR 0.73 95%CI 0.39-1.37). Compared to the BSC arm, elderly patients treated with CETUX had a non-significant increase in OS (8.0m vs 5.1m, p = 0.11). In patients treated with CETUX, grade 3/4 AEs were similar between age groups, however elderly patients had a faster deterioration in global QoL than younger patients (3.6m vs 5.7m p = 0.046). In CO.20, younger patients had longer OS than elderly (9.2m vs 7.6m, p = 0.02; HR 0.81 95% 0.68-0.97, p = 0.02). AEs in the BRIV+CETUX arm were higher in the elderly than young (88% vs 77%, p = 0.03). Both young and elderly treated with BRIV+CETUX had more rapid decreases in global QoL than the CETUX arm. Conclusions: Age was neither prognostic nor predictive of response to targeted therapy in the single agent CO.17 trial. In CO.20, age conferred a worse prognosis. Elderly patients who are eligible for clinical trials may garner similar survival benefits as younger patients with single agent therapy, but may not derive the same improvement in QoL.
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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 | 0.004 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".