title: PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer.
abstract: OBJECTIVE
  To evaluate panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer (mCRC). A prespecified secondary objective was to assess treatment effects in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS.
  
  
  METHODS
  Patients with WT KRAS exon 2 tumors were randomly assigned at a one-to-one ratio to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and safety.
  
  
  RESULTS
  Of 285 randomly assigned patients, 278 received treatment. In the WT KRAS exon 2 intent-to-treat group, PFS was similar between arms (hazard ratio [HR], 0.87; 95% CI, 0.65 to 1.17; P = .353). Median OS was 34.2 and 24.3 months in the panitumumab and bevacizumab arms, respectively (HR, 0.62; 95% CI, 0.44 to 0.89; P = .009). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS), PFS favored the panitumumab arm (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). Median OS was 41.3 and 28.9 months (HR, 0.63; 95% CI, 0.39 to 1.02; P = .058) in the panitumumab and bevacizumab arms, respectively. Treatment discontinuation rates because of adverse events were similar between arms.
  
  
  CONCLUSIONS
  PFS was similar and OS was improved with panitumumab relative to bevacizumab when combined with mFOLFOX6 in patients with WT KRAS exon 2 tumors. Patients with WT RAS tumors seemed to experience more clinical benefit with anti-epidermal growth factor receptor therapy.
authors.affiliation: Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA. lschwartzberg@westclinic.com.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Schwartzberg
authors.affiliation: Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.affiliation: Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA.
authors.forename: Meinolf
authors.initials: M
authors.lastname: Karthaus
authors.affiliation: Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Fasola
authors.affiliation: Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Canon
authors.affiliation: Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA.
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
authors.affiliation: Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.affiliation: Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Oliner
authors.affiliation: Lee S. Schwartzberg, West Clinic, Memphis, TN; Fernando Rivera, Hospital Universitario Marques de Valdecilla, Santander, Spain; Meinolf Karthaus, Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany; Gianpiero Fasola, University Hospital Santa Maria della Misericordia, Udine, Italy; Jean-Luc Canon, Grand Hopital de Charleroi, Charleroi, Belgium; J. Randolph Hecht, David Geffen School of Medicine at University of California Los Angeles, Los Angeles; and Hua Yu, Kelly S. Oliner, and William Y. Go, Amgen, Thousand Oaks, CA.
authors.forename: William Y
authors.initials: WY
authors.lastname: Go
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005091:Exons / 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 / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077544:Panitumumab; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000068258:Bevacizumab; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002955:Leucovorin; D005472:Fluorouracil