title: KRAS mutation as the biomarker of response to chemotherapy and EGFR-TKIs in patients with advanced non-small cell lung cancer: clues for its potential use in second-line therapy decision making.
abstract: OBJECTIVE
  In patients with non-small cell lung cancer (NSCLC), knowledge of the epidermal growth factor receptor (EGFR) mutation status is fundamental for selecting the treatment involving EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Little information is available regarding the response and progression-free survival (PFS) in platinum-based chemotherapy (CT) versus EGFR-TKIs in the presence or absence of KRAS mutation, particularly in patients without EGFR mutation.
  
  
  METHODS
  From 2007 to 2010, 353 patients with NSCLC were treated with first-line CT, EGFR-TKIs were used in the second or third line of treatment. Tests were performed for EGFR and KRAS mutation and the results of the mutations were obtained 3 to 4 months after the start of the treatment. We analyzed clinical characteristics, mutation profile, response and PFS to CT and EGFR-TKIs, and overall survival. The protocol is registered with ClinicalTrials.gov, number NCT01023828.
  
  
  RESULTS
  Presence of the wild-type (WT) KRAS was independently associated with increased response rate to first-line CT when compared with KRAS mutation (41.4% vs. 14.7%; P=0.001). The EGFR mutation (57.8% vs. 11.7%; P<0.001) and WT-KRAS (39.6% vs. 3.3%; P=0.001) were associated with the EGFR-TKIs response. PFS of patients with WT-EGFR and KRAS mutation treated with EGFR-TKIs was shorter when compared with patients with WT-EGFR and WT-KRAS (P<0.001).
  
  
  CONCLUSIONS
  KRAS mutation status is a good biomarker for response to EGFR-TKIs in patients with NSCLC. KRAS mutational status could impact the decision to give CT or EGFR-TKIs as a second line of treatment to patients with NSCLC, particularly in patients with WT-EGFR.
authors.affiliation: *Laboratory of Experimental Oncology †Thoracic Oncology Clinic §Department of Pathology #Laboratory of Translational Medicine, Instituto Nacional de Cancerología (INCan) ‡Department of Pathology, Instituto Nacional de Enfermedades Respiratorias (INER), Tlalpan, México, D.F ∥Boehringer Ingelheim, Barrio Xaltocan, Xochimilco, México City, México ¶Clinical and Translational Oncology Group, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
authors.forename: Alma D
authors.initials: AD
authors.lastname: Campos-Parra
authors.forename: Carlos
authors.initials: C
authors.lastname: Zuloaga
authors.forename: María Eugenia Vazquez
authors.initials: ME
authors.lastname: Manríquez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Avilés
authors.forename: Jose
authors.initials: J
authors.lastname: Borbolla-Escoboza
authors.forename: Andrés
authors.initials: A
authors.lastname: Cardona
authors.forename: Abelardo
authors.initials: A
authors.lastname: Meneses
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D018631:ras Proteins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D014747:Vinblastine; D016190:Carboplatin; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine