Monoclonal antibodies targeting epidermal growth factor receptor and vascular endothelial growth factor with a focus...

To provide an overview of recent clinical trials with monoclonal antibodies targeting epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in head and neck cancer (HNC) and in other tumors. To discuss future therapeutic strategies.

Cetuximab, a chimeric monoclonal antibody targeting EGFR, has induced improved locoregional control and survival in combination with radiotherapy in a phase III study in locally advanced inoperable HNC. The recent Bowel Oncology with Cetuximab Antibody (BOND) study has shown that the combination of irinotecan and cetuximab yields a better response rate and a longer time to progression with respect to cetuximab monotherapy in irinotecan-refractory metastatic colorectal cancer, pointing to both a cetuximab single-agent activity and a cetuximab potential for reversal of irinotecan resistance. Non-small cell lung cancer and pancreatic cancer represent further areas for cetuximab development. Bevacizumab is a humanized monoclonal antibody that targets VEGF. It is the first antiangiogenic drug to have induced a survival advantage in cancer therapy, within a randomized trial of irinotecan, 5-fluorouracil, leucovorin (IFL) combined with bevacizumab or placebo in metastatic colorectal cancer. The use of bevacizumab in HNC is supported by preclinical evidence of an angiogenic loop; a few clinical trials are exploring the feasibility and the therapeutic potential of a combination of bevacizumab and EGFR-targeted drugs.

Monoclonal antibodies targeting EGFR and VEGF represent exciting therapeutic strategies that should be further evaluated both in combination with drugs acting on the same target at a different level and in combination with other antisignaling agents acting on different pathways.