Trastuzumab in the treatment of non-small cell lung cancer

Trastuzumab is a humanized monoclonal antibody that binds to human epidermal growth factor-2 (HER2) and is approved by the US Food and Drug Administration for the treatment of advanced breast cancer that overexpresses HER2/neu protein. Preclinical data suggests a role for trastuzumab in the treatment of non-small cell lung cancer (NSCLC). HER2 protein is overexpressed in 20% to 66% of resected NSCLC tumors, and has been shown to predict poor patient outcome in multiple series. Experiments with NSCLC cell lines show that HER2 overexpression increases chemoresistance, invasiveness, and metastatic potential of the cells. In mouse xenograft experiments, trastuzumab halts tumor growth and is synergistic with cytotoxic chemotherapy. Ongoing phase II trials are showing that trastuzumab can be added to standard chemotherapy in the treatment of patients with advanced NSCLC without additional toxicity, and with promising efficacy. Whether trastuzumab will show a clear benefit for patients with NSCLC, either alone or in combination with established chemotherapy, remains to be proven in phase III testing.