High expression of epidermal growth factor receptor (EGFR) can predict survival benefit from cetuximab (Erbitux) added to first-line chemotherapy in patients with advanced non–small cell lung cancer (NSCLC). The identification of high EGFR expression as a tumor biomarker follows findings from the phase III First-Line ErbituX in Lung Cancer (FLEX) study that showed adding cetuximab to cisplatin and vinorelbine significantly improved overall survival compared to chemotherapy alone.
Tumor cell expression of EGFR was an eligibility criterion for the FLEX study, and the current analysis used FLEX data on the intensity and frequency of membrane immunohistochemistry staining to generate EGFR scores of 0 to 300 for assessable patients. The selected threshold was 200, with scores < 200 considered low and > 200 high.
Tumor EGFR immunohistochemistry data were available for 1,121 (99.6%) of 1,125 patients from the FLEX study intention-to-treat population. “High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients,” the investigators reported in The Lancet Oncology. For patients with high EGFR expression, overall survival was longer (median, 12.0 months) in the chemotherapy-plus-cetuximab group than in the chemotherapy-alone group (median, 9.6 months), “with no meaningful increase in side effects,” the authors noted. No corresponding survival benefit was found for patients with low EGFR expression. “A treatment interaction test assessing the difference in the [hazard ratios] for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (P = .044),” the investigators stated.
Based on their findings, the investigators believe that “high EGFR expression might now be applied clinically as a predictive biomarker to identify patients with advanced NSCLC who will benefit from the addition of cetuximab to first-line chemotherapy.”
Merck KGaA provided funding for the study.■
Pirker R, et al: Lancet Oncol 13:33-42, 2012.