title: Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC).
  
  
  METHODS
  154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression.
  
  
  RESULTS
  Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease. Median response duration was longer in RAS WT (13.0 months) vs RAS MT (5.8 months) (hazard ratio (HR): 0.16). Median progression-free survival was longer in RAS WT vs MT (11.2 vs 7.3 months; HR, 0.37) and was also longer in RAS WT/BRAF WT vs RAS or BRAF MT (13.2 vs 6.9 months; HR, 0.25). Incidence of adverse events was similar regardless of RAS/BRAF status, and no new safety signals were noted. Among patients with RAS WT tumours, ORR was 67% with high AREG expression and 38% with low AREG expression.
  
  
  CONCLUSIONS
  First-line panitumumab+FOLFIRI was associated with favourable efficacy in patients with RAS WT and RAS WT/BRAF WT vs MT mCRC tumours and was well tolerated.
authors.affiliation: Klinikum Neuperlach/Klinikum Harlaching, Oskar-Maria-Graf-Ring 51, D81737 Munich, Germany.
authors.forename: Meinolf
authors.initials: M
authors.lastname: Karthaus
authors.affiliation: Universitätsmedizin Mannheim, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hofheinz
authors.affiliation: Institut Sainte-Catherine GI and Liver Cancer Unit, 84 000 Avignon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mineur
authors.affiliation: Oncology Clinic, Västmanland's Hospital, 721 89 Västerås, Sweden.
authors.forename: Henry
authors.initials: H
authors.lastname: Letocha
authors.affiliation: IIIrd Medical Department, Paracelsus Medical University Salzburg and CCCIT Salzburg Cancer Research Institute, Müllner Hauptstrasse 45, 5020 Salzburg, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.affiliation: Klinikum Wels-Grieskirchen, Grieskirchner Straße 42, A-4600 Wels, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Thaler
authors.affiliation: Central Hospital, Strandvägen 8, 35185 Växjö, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Fernebro
authors.affiliation: Formerly of Amgen Inc., 1 Amgen Center Dr MS 30E-2-C, Thousand Oaks, CA 91320, USA.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Oliner
authors.affiliation: Amgen Inc., 1 Amgen Center Dr MS 30E-2-C, Thousand Oaks, CA 91320, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Boedigheimer
authors.affiliation: Amgen Inc., 1 Amgen Center Dr MS 30E-2-C, Thousand Oaks, CA 91320, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Twomey
authors.affiliation: Amgen Inc., 1 Amgen Center Dr MS 30E-2-C, Thousand Oaks, CA 91320, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Amgen GmbH, Dammstrasse 23, 6301 Zug, Switzerland.
authors.forename: Gaston
authors.initials: G
authors.lastname: Demonty
authors.affiliation: Onkologie Klinikum Oldenburg, Rahel-Straus-Str. 10, 26133 Oldenburg, Germany.
authors.forename: Claus-Henning
authors.initials: CH
authors.lastname: Köhne
mesh_terms: D066258:Amphiregulin / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D000077544:Panitumumab; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics*
chemical_list: D066258:Amphiregulin; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000077544:Panitumumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin