Clinical and molecular predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer

Up to 10% of patients with non-small cell lung carcinoma (NSCLC) achieve an objective response to EGFR tyrosine kinase inhibitors (EGFR-TKI) such as erlotinib or gefitinib. This rate of response is related to non-smoker status, female gender, adenocarcinoma subtype, and Asian ethnicity. Molecular analysis showed that EGFR tyrosine kinase domain somatic mutations appear to be a strong predictor of response to EGFR-TKI. The L858R point mutation and the E746-A750 deletion represent 90% of the mutations encountered in responding patients. The amplification of EGFR gene also seems to be predictive of the response to EGFR-TKI, whereas T790M point mutation induces secondary resistance to EGFR-TKI. Nevertheless, objective responses or strong long-term stabilizations are observed in patients without any EGFR abnormality. Thus, the assessment of the EGFR status in patients with NSCLC remains controversial for clinical practice. The assessment of EGFR abnormalities should be targeted to identify reliable biomarkers of the NSCLC response to EGFR-TKI. This review presents the current knowledge on predictive biomarkers of NSCLC response to EGFR-TKI and the methods available for the assessment of EGFR status.