Response to First-Line Chemotherapy in Patients With Non–Small-Cell Lung Cancer According to Epidermal Growth Factor Receptor and K-RAS Mutation Status

Abstract

BackgroundEpidermal growth factor receptor (EGFR)–targeted therapy has shown a favorable efficacy in patients with non–small-cell lung cancer (NSCLC). Conversely, K-RAS mutations were reported to have an adverse effect on the survival of patients with NSCLC. These studies suggest that the tumor biology of patients with EGFR or K-RAS mutations is different from that of patients with wild-type mutations. Therefore, we hypothesized that the response to cytotoxic chemotherapy may differ among patients with and without EGFR or K-RAS mutations. MethodsA total of 229 patients with advanced NSCLC who received platinum doublet chemotherapy were included in this retrospective study, and their clinical outcomes were analyzed according to EGFR and K-RAS mutation status. ResultsEGFR and K-RAS mutations were found in 52.4% and 27.9% of patients, respectively. Progression-free survival (PFS) was significantly higher in patients with EGFR mutations than in patients with wild-type EGFR (P = .008), and multivariate analysis showed that EGFR mutation was an independent factor to chemotherapy (P = .01). Among the patients with EGFR mutations, the disease control rate for docetaxel was higher than for gemcitabine-based therapy (P = .031). In addition, docetaxel or vinorelbine showed a longer PFS than gemcitabine-based chemotherapy in patients with EGFR mutations (P = .033 and P = .028). However, no similar differences were found according to the K-RAS mutations. ConclusionsEGFR, but not K-RAS mutation, is associated with improved survival time to platinum-based chemotherapy. In patients with EGFR mutations, PFS for docetaxel and gemcitabine was higher than for vinorelbine-based chemotherapies. The predictive meaning of EGFR mutation for chemotherapy should be further investigated.