Epidermal Growth Factor Receptor Antagonists in Pancreatic Cancer

Pancreatic cancer is the fourth leading cause of cancer-related death in North America and is associated with an extremely bleak prognosis. Advances in the treatment of this devastating disease will require novel approaches. A key therapeutic strategy is inhibition of the epidermal growth factor receptor (EGFR). The EGFR is overexpressed in pancreatic cancer and is associated with poor prognosis. This article summarizes current knowledge of the role of EGFR antagonists in pancreatic cancer and focuses on the preclinical background and EGFR inhibitors in clinical development including erlotinib, gefitinib, cetuximab, and matuzumab. Erlotinib in combination with chemotherapy and radiation has encouraging antitumor activity in locally advanced pancreatic cancer. A phase II trial of cetuximab and gemcitabine in advanced pancreatic cancer showed promising activity and 1-year survival. Proof of principle for EGFR inhibition in this disease was provided by a phase III trial in advanced pancreatic cancer that demonstrated a survival advantage with erlotinib in combination with gemcitabine compared with placebo plus gemcitabine. Current research efforts are aimed at determining predictive factors for response to EGFR inhibitors, defining the role of EGFR blockade in early stages of disease, and exploring combinations with other molecular-targeted approaches.