The addition of monoclonal antibodies to chemotherapy in metastatic early-onset colorectal cancer: A comparative effectiveness study using real-world data.
Bibliographic record
Abstract
e15580 Background: The incidence of early-onset colorectal cancer (eoCRC) in adults under the age of 50 years is rising in Canada and the United States. Despite this trend, eoCRCs account for only ~10% of colorectal cancer diagnoses and are underrepresented in trials of novel chemotherapies and targeted agents. The benefit of adding monoclonal antibodies to chemotherapy for stage IV disease remains uncertain, with limited knowledge on factors beyond RAS genes that influence treatment response. Given the distinct molecular features of eoCRC tumours compared to later-onset tumours, identifying optimal treatment regimens for metastatic eoCRC population is crucial. Objective: This project leveraged existing real-world data to investigate the effectiveness of initiating first line combination chemotherapy vs. combination chemotherapy plus monoclonal antibodies in stage IV eoCRC in Alberta. Methods: We conducted a population-based, retrospective cohort study including all patients aged 18to 49 years in Alberta diagnosed with metastatic CRC from 2004 to 2020. Data from electronic medical records, administrative data claims, and vital statistics were merged. Observational data were used to emulate a target trial comparing the initiation of any combination chemotherapy (fluorouracil/capecitabine plus oxaliplatin regimens) vs. combination chemotherapy plus monoclonal antibodies (bevacizumab/cetuximab/panitumumab) within 16 weeks of diagnosis. The primary outcome was overall survival. Follow-up began at time of diagnosis and patients were followed until death, last known date of contact with the healthcare system, or administrative end of follow-up (April 2022), whichever occurred first. To address time-varying selection bias and confounding, marginal Cox models with inverse-probability censoring weights and artificial cloning were employed to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Results: A total of 674 patients were included, where 313 (46%) initiated chemotherapy and 146 (22%) initiated chemotherapy plus monoclonal antibodies. Patients initiating monoclonal antibodies were more likely to have proximal tumours (34.2% vs. 21.1%) and less likely to receive surgery (41.1% vs. 52.1%) and radiation (4.8% vs 24%) than patients initiating chemotherapy alone. The risk of death from any cause death was 5% higher (HR:1.05; 95%CI: 0.88-1.26) among those who initiated monoclonal antibodies relative to those who did not, but statistical significance was not achieved. Conclusions: Our study did not demonstrate survival benefits of initiating first line monoclonal antibodies in stage IV eoCRC, which is likely explained by the fact that survival depends on compliance and subsequent lines of therapy. We did not have access to RAS gene status, an important predictor of treatment response.
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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 | 0.016 | 0.023 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| 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".