title: 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: BACKGROUND
  Epidermal 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  EGFR 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.
  
  
  CONCLUSIONS
  EGFR, 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.
authors.affiliation: Department of Thoracic Surgery, Second Hospital of Shandong University, Jinan, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Dong
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Zhao
authors.forename: Yingtao
authors.initials: Y
authors.lastname: Hao
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Wei
authors.forename: Qiuwei
authors.initials: Q
authors.lastname: Yin
authors.forename: Jiajun
authors.initials: J
authors.lastname: Du
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D004252:DNA Mutational Analysis; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine
keywords: Chemotherapy; EGFR mutation; K-RAS mutation; NSCLC