title: EGFR-directed monoclonal antibodies in non-small cell lung cancer: how to predict efficacy?
abstract: Cetuximab improved survival when added to first-line platinum-based chemotherapy in patients with advanced non-small cell lung cancer. In order to determine those patients who will derive the greatest benefit from the addition of cetuximab, the associations of clinical and tumor features with clinical outcome were determined. High EGFR expression of tumor cells based on an immunohistochemistry score was shown to predict benefit of cetuximab. Among patients with high EGFR expression, the hazard ratio for death was 0.73 in favor of chemotherapy plus cetuximab compared to chemotherapy alone. Among patients with low EGFR expression, no difference in survival was observed between patients treated with chemotherapy plus cetuximab compared to those treated with chemotherapy alone. The treatment interaction test was significant. KRAS mutation status and EGFR copy numbers were without predictive value. Patients with EGFR-activating mutations in their tumors had longer survival independent of the use of cetuximab. In conclusion, EGFR expression levels lend themselves as predictive biomarkers for the selection of those patients who will benefit from the addition of cetuximab to first-line chemotherapy with platinum-based doublets.
authors: Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria.
authors: Robert
authors: R
authors: Pirker
keywords: EGF receptor; biomarker; cetuximab; lung cancer; monoclonal antibody; targeted therapy