The addition of monoclonal antibodies to chemotherapy in metastatic early-onset colorectal cancer: A comparative effectiveness study using real-world data.

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.