The evolving role of cetuximab in non-small cell lung cancer.

Cetuximab is a monoclonal antibody directed against the ligand binding site in the extracellular domain of the epidermal growth factor receptor (EGFR). Cetuximab is currently approved for the treatment of patients with refractory colorectal cancer. In locally advanced head and neck carcinoma, cetuximab in combination with radiotherapy significantly improved survival compared with radiotherapy alone, and this treatment awaits Food and Drug Administration approval. In previously treated non-small cell lung cancer, single-agent cetuximab produced an objective response in 3 of 66 eligible patients and a median survival of 8.1 months. Treatment was well tolerated, with skin rash as the principal toxicity. The vast majority of patients (60 of 66) expressed EGFR by immunohistochemistry but no correlation existed between response and EGFR mutations. Two single-arm phase II trials testing cetuximab in combination with a platinum-based doublet in previously untreated patients showed responses in the range of 26% to 29%, with median survival times of 10 to 11 months. A European phase II randomized trial tested cisplatin/vinorelbine with or without cetuximab as first-line therapy in 86 patients with advanced non-small-cell lung cancer. Overall efficacy was slightly superior in the cetuximab arm and a phase III trial is currently ongoing to definitively determine the role of cetuximab in this setting.