Cetuximab in the management of colorectal cancer

Cetuximab, a chimeric IgG1 monoclonal antibody that targets the ligand-binding domain of the epidermal growth factor receptor (EGFR), is active in metastatic colorectal cancer (mCRC). As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. More recent studies show promising activity in second-line treatment after oxaliplatin-based therapy failure, and with first-line chemotherapy, where increased response rates seen with adding cetuximab to first-line therapy for mCRC may increase chances for curative surgery in a population for whom the therapy goal would otherwise be palliative. Cetuximab is generally well tolerated; common toxicities are acne-form rash and hypomagnesemia. Rash intensity is associated with clinical efficacy, and in the future, may be used as a marker for optimal drug exposure. Cetuximab activity in mCRC is not correlated with EGFR expression, and consequently other markers will be needed to identify the most likely responders. Cetuximab has clinically emerged as a core agent, along with 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab, for overall mCRC management to optimize survival. Ongoing studies are exploring best combinations of cetuximab with these other agents to maximize patient outcome.