Cetuximab in non-small-cell lung cancer
Cetuximab is a chimeric monoclonal antibody that is directed towards the epidermal growth factor receptor (EGFR). It has been evaluated in combination with first-line chemotherapy in several phase II and two phase III trials in patients with advanced NSCLC. The phase III FLEX trial demonstrated improved survival for cetuximab combined with cisplatin plus vinorelbine compared to chemotherapy alone. The BMS099 trial failed to show a significant improvement in progression-free survival but resulted in a hazard ratio for death similar to the one seen in the FLEX trial. A meta-analysis of four randomized trials confirmed the efficacy of cetuximab when added to chemotherapy. EGFR expression levels based on an immunohistochemistry score have recently been shown to predict benefit from cetuximab in the FLEX trial. In patients with high EGFR expression, patients had prolonged survival when treated with chemotherapy plus cetuximab compared to chemotherapy alone. In patients with low EGFR expression, outcome was not different between the two treatment arms. Thus platinum-based chemotherapy combined with cetuximab represents a new treatment option for patients with advanced NSCLC and high EGFR expression in their tumors. Cetuximab is also evaluated in combination with chemoradiotherapy in patients with stage III NSCLC.