Clinical Implications of KRAS Mutations in Lung Cancer Patients Treated with Tyrosine Kinase Inhibitors: An Important Role for Mutations in Minor Clones

摘要: Mutations inducing resistance to anti-epidermal growth factor receptor (EGFR) therapy may have a clinical impact even if present in minor cell clones which could expand during treatment. We tested this hypothesis lung cancer patients treated with tyrosine kinase inhibitors (TKIs). Eighty-three adenocarcinoma erlotinib or gefitinib were included study. The mutational status of KRAS and EGFR was investigated by direct sequencing (DS). mutations also assessed mutant-enriched (ME-sequencing). DS detected 16 (19%) 83 tumors; ME-sequencing identified all the but 14 additional tumors, for total 30 (36%) 83. significantly correlated TKIs (P = .04 P .004, respectively) affected progression-free survival (PFS) overall (OS). However, predictive power higher than that obtained (hazard ratio [HR] 2.82, .0001 vs HR 1.98, .04, respectively, OS; 2.52, .0005 2.21, .007, PFS). Survival outcome harboring clones, only ME-sequencing, did not differ from DS. Only remained an independent at multivariate analysis. important on response EGFR-TKI. use sensitive detection methods allow more effectively identify treatment-resistant patients.