Optimal integration of EGFR inhibitors in advanced colorectal cancer

The epidermal growth factor receptor (EGFR) pathway plays a key role in the pathogenesis of colorectal cancer and has become an important target in the treatment of metastatic disease. Although initial studies were in relapsed and refractory settings, ample data have now emerged to support the use of cetuximab and panitumumab with chemotherapy earlier in the disease course. Their use has become more refined with the emergence of KRAS mutation status as a predictive marker, and investigation continues into additional molecular markers to further target the use of these agents to those most likely to benefit. Attempts to combine EGFR antibodies with bevacizumab have produced increased toxicity without improvement in outcomes, and several studies recently suggest that irinotecan may be a better partner for EGFR antibodies than is oxaliplatin. The high response rates seen in front-line therapy of KRAS wild-type patients suggest a role for incorporating these agents into the neoadjuvant treatment of patients with liver-only metastases, and this continues to be an active area of investigation, as does direct comparison of these agents with bevacizumab in the first-line setting.