title: Impact of the specific mutation in KRAS codon 12 mutated tumors on treatment efficacy in patients with metastatic colorectal cancer receiving cetuximab-based first-line therapy: a pooled analysis of three trials.
abstract: OBJECTIVE
  This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Overall, 119 patients bearing a KRAS mutation in codon 12 were evaluated. All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO KRK-0104 or AIO KRK-0306 trials.
  
  
  RESULTS
  Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations (overall survival 23.3 vs. 14-18 months; hazard ratio 0.66, range 0.43-1.03). An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab.
  
  
  CONCLUSIONS
  The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy.
authors.affiliation: Department of Medicine III, University Hospital Grosshadern, University of Munich, Munich, Germany. dominik.modest@med.uni-muenchen.de
authors.forename: Dominik P
authors.initials: DP
authors.lastname: Modest
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodowicz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
authors.forename: Ruediger P
authors.initials: RP
authors.lastname: Laubender
authors.forename: Janja
authors.initials: J
authors.lastname: Ocvirk
authors.forename: Galina
authors.initials: G
authors.lastname: Kurteva
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Papai
authors.forename: Regina
authors.initials: R
authors.lastname: Knittelfelder
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D000068818:Cetuximab; D003062:Codon / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005858:Germany; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009154:Mutation; D016017:Odds Ratio; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D018631:ras Proteins / Q000187:drug effects / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003062:Codon; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin