A high level of epidermal growth factor receptor (EGFR) expression in non-small cell lung cancer is a good predictor for increased survival with cetuximab added to first-line chemotherapy, according to a major study reported at the World Conference on Lung Cancer (4 July; Amsterdam, The Netherlands).

The phase III FLEX study has previously shown that adding cetuximab to first-line, platinum-based chemotherapy significantly improves overall survival in patients with EGFR-expressing advanced non-small cell lung cancer. Researchers have now analysed the results further by looking at the association between EGFR expression in patients' tumours and their clinical outcome. They assessed the proportion of tumour cells expressing EGFR and the intensity of staining using immunohistochemistry.

Results from 1121 of the patients taking part in the FLEX study showed that 31% had high tumour EGFR expression (defined as > 200 on a scale of 0-300). Overall survival was significantly prolonged when cetuximab, a monoclonal antibody directed against EGFR, was added to chemotherapy in this group, compared to patients treated with chemotherapy alone (median 12.0 vs 9.6 months; hazard ratio 0.73; p=0.011). In contrast, there was no survival benefit with cetuximab for patients with low EGFR expression (< 200).

One-year survival was 50% in patients with high EGFR expression treated with cetuximab plus chemotherapy, compared to 37% in those given chemotherapy alone. Two-year survival was also higher (24% vs 15%).

"This new analysis of the FLEX study has allowed us to identify which patients with non-small cell lung cancer are most likely to benefit from treatment with cetuximab in the first-line setting," said Robert Pirker, professor of medicine at the Medical University of Vienna, Austria, and lead investigator of the study.

"This is the first trial to show that EGFR is a disease-related biomarker that can be used to tailor cetuximab treatment to patients most likely to derive a clinically meaningful benefit," he said, adding that immunohistochemistry is a simple and established analytical method that is widely available in pathology departments.

A treatment interaction test assessing the difference in the hazard ratios for overall survival between patients with high and low expression of EGFR was significant (p=0.044).

Susan Mayor PhD
Susan Mayor PhD, freelance medical journalist, London

Reference
Pirker R, Paz Ares L, Eberhardt W et al. Epidermal growth factor receptor (EGFR) expression as a predictor of survival for first-line chemotherapy plus cetuximab in FLEX study patients with advanced non-small cell lung cancer (NSCLC). WCLC 2011; abstract 1557