The place of targeted therapy in the patient management of non-small cell lung cancer.

Abstract

There is much interest in the use of targeted therapies for the management of non-small cell lung cancer (NSCLC). To date, four targeted therapies - bevacizumab, cetuximab, erlotinib and gefitinib - have been investigated in randomised trials, in the treatment of advanced NSCLC. In the first-line setting, bevacizumab has been shown to significantly prolong survival when added to carboplatin/paclitaxel, as demonstrated in a large phase III study. However, issues of toxicity limit this treatment regimen to selected patients. The addition of bevacizumab to gemcitabine/cisplatin will be reported at ASCO 2007. The addition of cetuximab to cisplatin/vinorelbine has also been shown to improve survival in a randomised phase II study. Erlotinib has been investigated as monotherapy in first-line chemo-naïve patients and has demonstrated objective response rates of 10-23%. However, in a study comparing erlotinib versus chemotherapy, the outcome was less favourable for patients who had received erlotinib. Erlotinib monotherapy has also been investigated in recurrent disease, and has been shown to improve overall survival over that achieved with placebo. The greatest benefit was observed in never-smokers with epidermal growth factor receptor-positive tumours. In a further phase II randomised study, the effect of combining two targeted therapies has been investigated. This study compared erlotinib/bevacizumab versus bevacizumab/chemotherapy versus chemotherapy alone. Both regimens including targeted therapy were comparable and superior to chemotherapy alone. However, these are preliminary data and further research is required to clarify the role of targeted therapies in the management of advanced NSCLC.