Molecular Selection of Patients for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer With Epidermal Growth Factor Inhibitors: Not Quite Ready for Prime Time

Abstract

Blockade of the epidermal growth factor (EGF) pathway through inhibition of EGF receptor (EGFR) is now well established in the treatment of non–small-cell lung cancer (NSCLC). 1 However, considerable debate remains regarding when to initiate EGFR inhibitor therapy, how best to select patients for treatment, and how EGFR markers should be incorporated into clinical decision making. With respect to this last issue, EGFR protein expression determined by immunohistochemistry (IHC),EGFR gene copy number determined by fluorescent in situ hybridization (FISH), and EGFR mutation status determined by gene sequencing or other more sensitive techniques may each contribute important information regarding which patients are likely to benefit from treatment. In NSCLC, small molecule inhibition of the EGFR tyrosine kinase pathway has been the most successful strategy to date, and two oral tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, have received approval for treatment in the second- and third-line setting. 2,3 In contrast, the addition of these agents to systemic chemotherapy in the first-line