title: KRAS mutations in advanced nonsquamous non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy have no predictive value.
abstract: BACKGROUND
  Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is thought to be related with dismal outcome for non-small-cell lung cancer (NSCLC) patients. The role of KRAS mutation as a predictor of response to chemotherapy for patients with metastatic NSCLC is poorly understood.
  
  
  METHODS
  From a retrospective database of two university hospitals, all patients with advanced, nonsquamous NSCLC treated with first-line platinum-containing chemotherapy were selected. Mutation analysis for KRAS was performed and the relation with response to chemotherapy was assessed. Secondary endpoints were its relation with response to progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  A total of 161 patients, 94 men and 67 women, were included in this study. Median age was 60 years. The majority of patients (79%) had stage IV disease, of which 60 patients (37%) had a KRAS mutation. Patients with a KRAS mutation had a similar response to treatment as patients with KRAS wild-type (wt) (p = 0.77). Median PFS in KRAS-mutated patients was 4.0 months versus 4.5 months in KRAS wt patients (hazard ratio = 1.3; [95% confidence interval, 0.9-1.8]; p = 0.16). Median OS in patients with KRAS mutation was 7.0 months versus 9.3 months in patients with KRAS wt (hazard ratio = 1.2; [95% confidence interval, 0.9-1.7]; p = 0.25). Type of KRAS mutation had no influence on response or outcome.
  
  
  CONCLUSIONS
  On the basis of our multicenter data presented here, we conclude that KRAS mutation is not predictive for worse response to chemotherapy, PFS, and OS in advanced NSCLC patients treated with platinum-based chemotherapy in first-line setting.
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wouter W
authors.initials: WW
authors.lastname: Mellema
authors.forename: Anne-Marie C
authors.initials: AM
authors.lastname: Dingemans
authors.forename: Erik
authors.initials: E
authors.lastname: Thunnissen
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Jules
authors.initials: J
authors.lastname: Derks
authors.forename: Daniëlle A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Robertjan
authors.initials: R
authors.lastname: Van Suylen
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D018631:ras Proteins / Q000235:genetics*
chemical_list: D005971:Glutamates; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D014747:Vinblastine; D006147:Guanine; D016190:Carboplatin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002945:Cisplatin; D000077235:Vinorelbine