title: Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study.
abstract: BACKGROUND
  The randomized phase II OPUS (Oxaliplatin and Cetuximab in First-Line Treatment of Metastatic Colorectal Cancer) study showed that tumor KRAS mutation status was predictive for outcome in patients receiving cetuximab plus FOLFOX-4 (oxaliplatin/5-fluorouracil/folinic acid) as first-line therapy for metastatic colorectal cancer (mCRC).
  
  
  METHODS
  The biomarker analysis was extended through the use of additional DNA samples extracted from stained tissue sections. KRAS and BRAF tumor mutation status was determined for new (and for BRAF, existing) samples using a PCR technique. Clinical outcome was reassessed according to mutation status. Overall survival data are presented.
  
  
  RESULTS
  Of 315 KRAS evaluable patient samples (93%), 179 tumors (57%) were KRAS wild type. Eleven of 309 (4%) KRAS/BRAF evaluable tumors (all KRAS wild type) carried BRAF mutations. The addition of cetuximab to FOLFOX-4 significantly improved progression-free survival (hazard ratio 0.567, P = 0.0064) and response (odds ratio 2.551, P = 0.0027) in patients with KRAS wild-type tumors. A favorable effect on survival was also observed.
  
  
  CONCLUSIONS
  These results confirm the efficacy of cetuximab plus FOLFOX-4 in the first-line treatment of patients with KRAS wild-type mCRC and confirm KRAS mutation status as an effective predictive biomarker. The small number of tumors with BRAF mutations precluded the drawing of definitive conclusions concerning the predictive or prognostic utility of this biomarker.
authors.affiliation: Department of Oncology, Hematology, BMT with Section Pneumology, University Hospital, Hamburg-Eppendorf, Germany. Electronic address: c.bokemeyer@uke.uni-hamburg.de.
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
authors.affiliation: City Clinical Hospital #4, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine.
authors.forename: I
authors.initials: I
authors.lastname: Bondarenko
authors.affiliation: Department of Medical Oncology, Hematology, Immunology, Rheumatology, and Pulmonology, South West German Comprehensive Cancer, University Hospital Tübingen, Tübingen, Germany.
authors.forename: J T
authors.initials: JT
authors.lastname: Hartmann
authors.affiliation: Division of Clinical Pharmacology and New Drugs, Istituto Europeo di Oncologia, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Department of Oncology, Hematology, BMT with Section Pneumology, University Hospital, Hamburg-Eppendorf, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Schuch
authors.affiliation: Global Clinical Development Unit-Oncology.
authors.forename: A
authors.initials: A
authors.lastname: Zubel
authors.affiliation: Global Clinical Development Unit-Oncology.
authors.forename: I
authors.initials: I
authors.lastname: Celik
authors.affiliation: Global Biostatistics, Merck KGaA, Darmstadt, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schlichting
authors.affiliation: Oncology, Rydygier Memorial Hospital, Krakow-Nowa Huta, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Koralewski
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 / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil