Patients with the most common form of lung cancer whose tumours express high levels of epidermal growth factor receptor (EGFR) are more likely to benefit from cetuximab treatment and live longer compared with those given chemotherapy alone, according to a study published in The Lancet Oncology.

The findings suggest that testing for level of EGFR expression could be used in everyday clinical practice to predict which non-small-cell lung cancer (NSCLC) patients are most likely to respond to cetuximab plus chemotherapy treatment and gain the greatest survival advantage.

"EGFR expression level is the first biomarker shown to be associated with survival benefit of a targeted therapy added to first-line chemotherapy in patients with advanced NSCLC", explains Robert Pirker from the Medical University of Vienna, Vienna, Austria, lead author of the study.

Currently, patients with advanced NSCLC have few treatment options and life expectancy is short. Thus, methods to identify which patients are most likely to benefit from new targeted drugs are urgently needed. To date, one of the most promising predictive pretreatment biomarkers is EGFR status.

In 2009, the First-Line Erbitux in Lung Cancer (FLEX) randomised trial reported that adding cetuximab to standard chemotherapy as a first-line treatment significantly improved survival in patients with NSCLC.

In the study reported today, researchers did a new analysis of the FLEX study data to assess whether the level of expression of EGFR was associated with response to cetuximab.

1121 of 1125 patients had tumour EGFR expression data and were included in the analysis. The researchers used a scoring system ranging from 0–300 to identify patients with high and low levels of the EGFR protein.

Findings showed that patients with high (scoring 200 and above) EGFR expression had an overall survival benefit from cetuximab without an increase in toxic side-effects. In this group, patients receiving cetuximab plus chemotherapy had median survival of 12 months and 24% were alive at 2 years, compared with 9.6 months and 15%, respectively, for those given chemotherapy alone.

In contrast, no difference in overall survival was noted between the two groups in patients with low (scoring less than 200) EGFR expression.

An overall survival benefit in the high EGFR expression group was noted in all major NSCLC histological subgroups assessed, including the two most common—squamous-cell carcinoma and adenocarcinoma.

The authors conclude: "We 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."

In a Comment, Fred Hirsch from the University of Colorado Cancer Center, Colorado, USA, and Roy Herbst from Smilow Cancer Hospital, New Haven, USA, say: "Clearly, the use of targeted drugs requires specific criteria for patient selection based on the assessment of a molecular target... Use of EGFR immunohistochemistry in the FLEX study seems to be an encouraging step towards personalised medicine for patient subgroups with advanced lung cancer who will potentially receive cetuximab."

Source:  The Lancet