title: Survival outcome according to KRAS mutation status in newly diagnosed patients with stage IV non-small cell lung cancer treated with platinum doublet chemotherapy.
abstract: BACKGROUND
  Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20-25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear.
  
  
  METHODS
  We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods.
  
  
  RESULTS
  All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7 mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58-2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48-1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01).
  
  
  CONCLUSIONS
  KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy.
authors.affiliation: Department of Medicine, Washington University Medical Center, St. Louis, MO, USA.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Brady
authors.affiliation: Ruth and Raymond Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: McNeill
authors.affiliation: Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Brendan
authors.initials: B
authors.lastname: Judy
authors.affiliation: Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Bauml
authors.affiliation: Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Evans
authors.affiliation: Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Roger B
authors.initials: RB
authors.lastname: Cohen
authors.affiliation: Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Corey
authors.initials: C
authors.lastname: Langer
authors.affiliation: Division of Pulmonary, Allergy and Critical Care, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Vachani
authors.affiliation: Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Charu
authors.initials: C
authors.lastname: Aggarwal
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D016190:Carboplatin / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000627:therapeutic use; D015143:Philadelphia; D016016:Proportional Hazards Models; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D043823:Taxoids / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D017239:Paclitaxel; D002945:Cisplatin
keywords: KRAS; bevacizumab; non-small cell lung cancer