Where to position monoclonal antibodies in first-line treatment of advanced colorectal cancer

The treatment of metastatic colorectal cancer with modern cytotoxic agents in combination with monoclonal antibodies against vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) has improved median overall survival from 6 months to almost 2 years. Uncertainty remains over the optimal chemotherapy combination and sequencing, and to which line of treatment monoclonal antibodies should be added. This article reviews the rationale and evidence for the use of monoclonal antibodies in the first-line treatment of metastatic colorectal cancer in both general and specific situations, and provides a perspective on how to position their use in contemporary practice.