title: Correlation between KRAS mutation status and response to chemotherapy in patients with advanced non-small cell lung cancer☆.
abstract: OBJECTIVE
  KRAS mutations are the most commonly found mutations in patients with non-small cell lung cancer (NSCLC) adenocarcinoma histology. The clinical implications of KRAS mutations in patients with advanced NSCLC are not well defined. We sought to determine if there is a correlation between KRAS mutation status, response to cytotoxic chemotherapy, and survival in patients with metastatic or recurrent NSCLC.
  
  
  METHODS
  Patients with metastatic or recurrent NSCLC and tumor mutation analyses were analyzed for response to conventional chemotherapy. The presence or absence of tumor mutations was assessed with the SNaPshot assay, which detects >40 somatic mutations in eight genes, including KRAS. ALK fluorescence in-situ hybridization analysis was done separately. Associations between KRAS mutation status and response to chemotherapy and survival were assessed.
  
  
  RESULTS
  We identified 80 patients with metastatic or recurrent NSCLC and a KRAS activating mutation, and we compared these patients to 70 patients who were pan negative (no detectable mutation by the SNaPshot assay and ALK negative). Patients with KRAS-mutant advanced NSCLC demonstrated a significantly shorter progression-free survival in response to first line chemotherapy (4.5 months versus 5.7 months, p=0.008) compared to pan-mutation negative patients. Overall survival was also significantly shorter in patients with KRAS-mutant advanced NSCLC compared to patients without KRAS activating mutations (8.8 months versus 13.5 months, p=0.038).
  
  
  CONCLUSIONS
  Within this single institution retrospective analysis, patients with advanced NSCLC and a KRAS activating mutation exhibited inferior responses to cytotoxic chemotherapy and decreased survival compared to patients with advanced NSCLC and no KRAS mutation.
authors.affiliation: Department of Pharmaceutical Sciences, Vanderbilt University Medical Center (VUMC) 1211 Medical Center Drive, Nashville, TN 37232, United States.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Hames
authors.affiliation: Department of Cancer Biostatistics, Vanderbilt-Ingram Cancer Center (VICC)/Vanderbilt University Medical Center (VUMC) 2220 Pierce Avenue, 625 Preston Research Building, Nashville, TN 37232, United States.
authors.forename: Heidi
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, 1211 Medical Center Drive, Nashville, TN 37232, United States.
authors.forename: Wade
authors.initials: W
authors.lastname: Iams
authors.affiliation: Department of Pharmaceutical Sciences, Vanderbilt University Medical Center (VUMC) 1211 Medical Center Drive, Nashville, TN 37232, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Aston
authors.affiliation: Department of Medicine/Division of Hematology-Oncology, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37232, United States; Department of Cancer Biology, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37232, United States.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lovly
authors.affiliation: Department of Medicine/Division of Hematology-Oncology, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37232, United States. Electronic address: leora.horn@vanderbilt.edu.
authors.forename: Leora
authors.initials: L
authors.lastname: Horn
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Chemotherapy; KRAS; Metastatic; Non-small cell lung cancer