title: Genetic and proteomic features associated with survival after treatment with erlotinib in first-line therapy of non-small cell lung cancer in Eastern Cooperative Oncology Group 3503.
abstract: BACKGROUND
  Serum proteomics and mutations in the epidermal growth factor receptor (EGFR) and KRAS have been associated with benefit after therapy with EGFR-targeted therapies in non-small cell lung cancer, but all three have not been evaluated in any one study.
  
  
  OBJECTIVE
  Pretreatment serum proteomics predicts survival in Western advanced non-small cell lung cancer patients with wild-type EGFR and independent of KRAS mutation status.
  
  
  METHODS
  We analyzed available biospecimens from Eastern Cooperative Oncology Group 3503, a single-arm phase II study of erlotinib in first-line advanced lung cancer, for proteomics signatures in the previously described serum matrix-assisted laser desorption ionization proteomic classifier (VeriStrat) as well as for KRAS and EGFR mutations.
  
  
  RESULTS
  Out of 137 enrolled patients, analyzable biologic samples were available on 102. Nine of 41 (22%) demonstrated KRAS mutations and 3 of 41 (7%) harbored EGFR mutations. VeriStrat classification identified 64 of 88 (73%) as predicted to have "good" and 24 of 88 (27%) predicted to have "poor" outcomes. A statistically significant correlation of VeriStrat status (p < 0.001) was found with survival. EGFR mutations, but not KRAS mutations, also correlated with survival.
  
  
  CONCLUSIONS
  The previously defined matrix-assisted laser desorption ionization predictor remains a potent and highly clinically significant predictor of survival after first-line treatment with erlotinib in patients with wild-type EGFR and independent of mutations in KRAS.
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Amann
authors.forename: Ju-Whei
authors.initials: JW
authors.lastname: Lee
authors.forename: Heinrich
authors.initials: H
authors.lastname: Roder
authors.forename: Julie
authors.initials: J
authors.lastname: Brahmer
authors.forename: Adriana
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: David P
authors.initials: DP
authors.lastname: Carbone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D040901:Proteomics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000627:therapeutic use*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins