title: Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 Trial.
abstract: OBJECTIVE
  National Cancer Institute of Canada Clinical Trials Group CO.17 demonstrated the antiepidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab improves overall and progression-free survival in patients with advanced, chemotherapy-refractory colorectal cancer (CRC), particularly in patients with wild-type KRAS tumors. This article reports the health-related quality-of-life (HRQL) outcomes from CO.17.
  
  
  METHODS
  Patients (N = 572) with pretreated EGFR-detectable advanced CRC were randomly assigned to cetuximab and best supportive care (BSC) or to BSC alone. HRQL primary end points assessed by the EORTC QLQ-C30 were physical function (PF) and global health status (GHS); mean changes from baseline to 8 and 16 weeks were assessed. Post hoc analysis by KRAS mutation status was performed.
  
  
  RESULTS
  Questionnaire compliance was 94% at baseline, but it declined differentially (67% v 47% for cetuximab v BSC at 16 weeks). PF change scores were -3.9 for cetuximab and -8.6 for BSC (P = .046) at 8 weeks and were -5.9 and -12.5 for cetuximab and BSC, respectively, (P = .027) at 16 weeks. GHS change scores were -0.5 and -7.1 (P = .008) at 8 weeks and were -3.6 and -15.2 (P = .008) at 16 weeks for cetuximab and BSC, respectively. In patients who had tumors with wild-type KRAS status, cetuximab resulted in less PF deterioration at 8 weeks (-0.7 v -7.2; P = .11) and 16 weeks (-3.4 v -13.8; P = .008) compared with BSC. Patients with wild-type status who received cetuximab experienced improved GHS at 8 weeks, whereas patients who received BSC alone deteriorated (3.2 v -7.7; P = .002). Cetuximab preserved GHS at 16 weeks (-0.2 v -18.1; P < .001). No significant differences were noted between study arms for patients with mutated KRAS tumors.
  
  
  CONCLUSIONS
  Cetuximab offers important HRQL and survival benefits for pretreated patients with advanced, wild-type KRAS CRC.
authors.affiliation: Cross Cancer Institute, Edmonton, Alberta, Canada. heathera@cancerboard.ab.ca
authors.forename: Heather-Jane
authors.initials: HJ
authors.lastname: Au
authors.forename: Christos S
authors.initials: CS
authors.lastname: Karapetis
authors.forename: Chris J
authors.initials: CJ
authors.lastname: O'Callaghan
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
authors.forename: John R
authors.initials: JR
authors.lastname: Zalcberg
authors.forename: Hagen
authors.initials: H
authors.lastname: Kennecke
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Shapiro
authors.forename: Sheryl
authors.initials: S
authors.lastname: Koski
authors.forename: Nick
authors.initials: N
authors.lastname: Pavlakis
authors.forename: Danielle
authors.initials: D
authors.lastname: Charpentier
authors.forename: David
authors.initials: D
authors.lastname: Wyld
authors.forename: Michael
authors.initials: M
authors.lastname: Jefford
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Knight
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Magoski
authors.forename: Michael D
authors.initials: MD
authors.lastname: Brundage
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Jonker
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011788:Quality of Life; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab