Introduction: The medical treatment options for advanced colorectal cancer have greatly increased in the past decade, with conventional chemotherapeutics (eg, oxaliplatin and irinotecan) and targeted agents (eg, the vascular endothelial growth factor [VEGF] antibody bevacizumab and the endothelial growth factor receptor [EGFR] antibodies cetuximab and panitumumab) becoming integrated in standard treatment algorithms. Although it is well established that adding one targeted agent to chemotherapy can enhance the effi cacy of therapy compared with chemotherapy alone, little information is available on combining both targeted approaches (ie, combining bevacizumab with an EGFR antibody). Data from a randomized phase 2 trial in a salvage therapy setting showed intriguing results for the dual antibody combination with or without irinotecan [1], so testing dual antibodies (added to standard chemotherapy in the fi rst-line setting) appear to be warranted. Recent data on the predictive value of KRAS mutations for the activity of EGFR antibodies [2] made a detailed subgroup analysis of any trial testing cetuximab or panitumumab mandatory.