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Selecting Patients for Treatment with Epidermal Growth Factor Tyrosine Kinase Inhibitors

Authors' Affiliation: Rush University Medical Center, Chicago, Illinois

Requests for reprints: Philip D. Bonomi, Division of Hematology-Oncology, Rush University Medical Center, 1725 West Harrison Street, Suite 821, Chicago, IL 60612. Phone: 312-942-5904; Fax: 312-942-3192; E-mail: philip_bonomi{at}rsh.net.

Identification of objective tumor regressions with epidermal growth factor receptor tyrosine kinases (EGFR TKI) in non–small cell lung cancer (NSCLC) patients has resulted in intense, worldwide clinical and basic research directed toward finding the optimal use of EGFR TKIs in NSCLC. EGFR TKI clinical trials have shown that higher response rates and longer survival are associated with specific patient characteristics and that using conventional chemotherapy simultaneously with EGFR TKIs in unselected patients does not increase survival. Molecular studies have revealed that EGFR-activating mutations and high EGFR gene copy number are frequently found in patients who have the best outcomes with EGFR TKIs. More recent studies suggest that KRAS mutations may identify the subset of patients who have the worst outcome with the EGFR TKI treatment. Currently, investigators are trying to determine the optimal approach to selecting patients for treatment with EGFR TKIs. Studies that have evaluated the potential predictive value of clinical features and/or molecular profiles in EGFR TKI-treated NSCLC patients are discussed in this review.