Clinical relevance of monoclonal antibodies in non small cell lung cancer

Targeted therapies with monoclonal antibodies have been shown to improve the outcome of non-small cell lung cancer (NSCLC). Current strategies focus on the blockade of growth factor receptors and the inhibition of angiogenesis. Epidermal growth factor receptor (EGFR)-directed monoclonal antibodies in combination with platinum-based first-line chemotherapy have shown promising efficacy in phase II trials. In a phase III trial, cetuximab combined with cisplatin/ vinorelbine resulted in superior survival compared to chemotherapy alone in patients with advanced EGFR-positive NSCLC. Inhibition of angiogenesis has also been successfully applied as a new treatment strategy. Bevacizumab added to palliative chemotherapy has improved progression-free survival in two phase III trials and overall survival in one of these trials in selected patients with advanced non-squamous cell lung cancer. Bevacizumab is now approved for selected patients with advanced NSCLC in combination with platinum-based chemotherapy. Figitumumab is a monoclonal antibody against the insulin-like growth factor-1 receptor (IGF-1R) which demonstrated activity in preclinical models of NSCLC and in a phase II trial. Because of these promising results, three randomized, open-label, international phase III trials of figitumumab in patients with locally advanced or metastatic NSCLC are in progress.