A retrospective on the inhibition of epidermal growth factor receptor as a therapeutic strategy for patients with relapsed metastatic colorectal cancer: impact on treatment of today's patients.

The epidermal growth factor receptor (EGFR) pathway is overexpressed in many colorectal cancers (CRCs) and is associated with a worse prognosis compared with tumors that do not express EGFR. The development of monoclonal antibodies against this receptor, including cetuximab and panitumumab, and small-molecule inhibitors against the tyrosine kinase protein has led to new therapeutic paradigms in the treatment of metastatic CRC (mCRC). The anti-EGFR monoclonal antibody cetuximab has been shown to reverse chemotherapy resistance in patients with irinotecan-refractory mCRC, to improve survival compared with best supportive care (BSC) alone, and to prolong progression free-survival (PFS) in the first- and second-line settings. Panitumumab prolongs PFS compared with BSC, and trials in the first- and second-line settings are ongoing. Clinical trials with tyrosine kinase inhibitors have yielded disappointing results. This article reviews the clinical trial evidence for treatment strategies based on EGFR inhibition in relapsed/refractory mCRC, mechanisms of resistance to EGFR agents, clinical uncertainties, and future directions.