High copy number of the epidermal growth factor receptor ( EGFR ) may be an effective predictor of Gefitinib ( Iressa ) efficacy in non–small-cell lung cancer.

Gefitinib is a selective inhibitor of EGFR tyrosine kinase, which is overexpressed in many cancers, including non–small-cell lung cancer ( NSCLC ).

A study, led by Fred R. Hirsch, from University of Colorado Cancer Center at Aurora, evaluated the relationship between EGFR gene copy number, EGFR protein expression, EGFR mutations, and Akt activation status as predictive markers for Gefitinib therapy in advanced NSCLC.

Amplification or high polysomy of the EGFR gene and high protein expression were statistically significantly associated with better response ( 36% versus 3%, mean difference = 34% ), disease control rate ( 67% versus 26%, mean difference = 40.6% ), time to progression ( 9.0 versus 2.5 months, mean difference = 6.5 months ), and survival ( 18.7 versus 7.0 months, mean difference = 11.7 months ).

EGFR mutations were also statistically significantly related to response and time to progression, but the association with survival was not statistically significant, and 40% of the patients with mutation had progressive disease.

In multivariable analysis, only high EGFR gene copy number remained statistically significantly associated with better survival ( hazard ratio, HR = 0.44 ).

Source: Journal of National Cancer Institute, 2005


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