Chronological survival improvement over time with oxaliplatin-based chemotherapy plus targeted agents in metastatic colorectal cancer: An ARCAD database study

Abstract

Introduction: The combination of oxaliplatin-based doublet chemotherapy and molecular targeted agents is the standard first-line treatment for metastatic colorectal cancer. However, the temporal evolution of associated treatment outcomes is unclear. We utilized Aide et Recherche en Cancérologie Digestive (ARCAD) data to evaluate the chronological changes in clinical outcomes associated with this regimen in metastatic colorectal cancer. Methods: An individual patient data meta-analysis was performed using data from 5424 patients enrolled in 13 randomized controlled trials within the ARCAD database between 2004 and 2017. Eligible patients received oxaliplatin-based chemotherapy combined with bevacizumab or anti-epidermal growth factor receptor antibodies. Intervals of 2004–2008, 2009–2013, and 2014–2017 were examined. Overall, progression-free, and post-progression survivals were analyzed using Kaplan–Meier and Cox proportional hazards models adjusted for key prognostic factors. Results: Median overall survival improved over time, from 21.4 months (2004–2008) to 28.6 months (2009–2013) and 29.7 months (2014–2017). Similar trends were observed for progression-free and post-progression survivals. Multivariable analysis confirmed the treatment period as an independent prognostic factor for overall and progression-free survivals. Subgroup analyses revealed improvements in overall survival for left-sided and RAS wild-type tumors, whereas minimal gains were found for right-sided or RAS-mutated tumors. Increased use of subsequent therapies contributed to prolonged post-progression survival. Conclusions: We demonstrated progressive improvements in survival outcomes for patients with metastatic colorectal cancer receiving first-line oxaliplatin-based chemotherapy plus molecular targeted agents. The findings highlight the importance of biomarker-driven treatment strategies and the evolving role of subsequent therapies in optimizing clinical outcomes.