Primary Tumor Location Implications on Biological Therapy in Metastatic Colorectal Cancer

Anti-epidermal growth factor receptors (anti-EGFRs) have been clinically proven to improve overall survival (OS) when combined with chemotherapy in the settings of extended RAS wild-type metastatic colorectal cancers. In addition, randomized phase III studies have confirmed the superiority of anti-EGFR therapy over bevacizumab in the front-line treatment of extended RAS wild-type metastatic colorectal cancer when it comes to response rate, and in select studies, OS. Recent updates from these clinical trials project convincing evidence that tumor sidedness is yet another predictive marker for response to anti-EGFR therapy. While left colonic RAS wild-type metastatic colorectal cancers derive major clinical benefit from anti-EGFR versus bevacizumab therapy, bevacizumab appears to have clear advantage in RAS wild-type metastatic right-sided tumors. In this review, we summarize recent reports from key clinical trials and their impact on day-to-day clinical practice.