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 irinotecanrefractory 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.