EGFR inhibition in NSCLC: the emerging role of cetuximab

Epidermal growth factor receptor expression has been shown to contribute to the growth and survival of tumor cells via several mechanisms. High levels of this expression are common in patients with non-small cell lung cancer and correlate with decreased survival. Two classes of epidermal growth factor receptor inhibitors are currently under investigation: tyrosine kinase inhibitors and monoclonal antibodies, including cetuximab. To date, results of phase II or III trials of tyrosine kinase inhibitors have yielded mixed results, with moderate activity but no increase in survival reported in patients with advanced non-small cell lung cancer. Recently reported results of phase II trials of cetuximab in combination with chemotherapy show the feasibility and activity of these combinations, with overall response rates of 22% to 53% in previously treated and untreated patients. The primary toxicity of epidermal growth factor receptor inhibitors is mild-to-moderate rash that is occasionally severe. In addition, hypersensitivity reactions are uncommonly reported with monoclonal antibodies, and orally administered tyrosine kinase inhibitors are associated with diarrhea that can be dose limiting. Combining epidermal growth factor receptor inhibitors with chemotherapy does not appear to increase chemotherapy-related toxicity. One tyrosine kinase inhibitor, ZD1839, has been associated with a low incidence of interstitial lung disease. Results to date suggest a potential role of epidermal growth factor receptor inhibition in non-small cell lung cancer, and investigation into the optimal use of these inhibitors continues.