title: Quality of life in patients with K-RAS wild-type colorectal cancer: the CO.20 phase 3 randomized trial.
abstract: BACKGROUND
  The CO.20 trial randomized patients with K-RAS wild-type, chemotherapy-refractory, metastatic colorectal cancer to receive cetuximab (CET) plus brivanib alaninate (BRIV) or CET plus placebo (CET/placebo).
  
  
  METHODS
  Quality of life (QoL) was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 at baseline and at 2, 4, 6, 8, 12, 16, and 24 weeks until disease progression. Predefined coprimary QoL endpoints were time to deterioration (first worsening from baseline of ≥ 10 points) on the Physical Function (PF) and Global (GHS) scales.
  
  
  RESULTS
  Of 750 randomized patients, 721 (358 of whom received CET/BRIV) were assessable for QoL. QoL compliance and baseline PF and GHS scores did not differ by treatment arm. The median time to deterioration was 1.6 months versus 1.1 months for GHS (P =.02) and 5.6 months versus 1.7 months for PF (P <.0001) favoring CET/placebo. Secondary analysis favored CET/placebo for QOL response on the PF, Cognitive Function, Fatigue, Nausea, Appetite, and Diarrhea scales. A greater percentage of patients on the CET/BRIV arm had PF worsening at 6 weeks (31% vs 17%). Clinical adverse events of ≥ grade 3 were more common with CET/BRIV than with CET/placebo, including fatigue (25% vs 11%), hypertension, rash, diarrhea, abdominal pain, dehydration, and anorexia.
  
  
  CONCLUSIONS
  Compared with CET/placebo, the combination of CET/BRIV worsened time to QoL deterioration for patients with K-RAS wild-type, chemotherapy-refractory, metastatic colorectal cancer on the PF and GHS scales of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. This result may be due to higher rates of fatigue and gastrointestinal adverse events.
authors.affiliation: Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.forename: Heather-Jane
authors.initials: HJ
authors.lastname: Au
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Shapiro
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Jonker
authors.forename: John R
authors.initials: JR
authors.lastname: Zalcberg
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Andrew
authors.initials: A
authors.lastname: Strickland
authors.forename: Rami
authors.initials: R
authors.lastname: Kotb
authors.forename: Mark
authors.initials: M
authors.lastname: Jeffery
authors.forename: Thierry
authors.initials: T
authors.lastname: Alcindor
authors.forename: Siobhan
authors.initials: S
authors.lastname: Ng
authors.forename: Muhammad
authors.initials: M
authors.lastname: Salim
authors.forename: Sabe
authors.initials: S
authors.lastname: Sabesan
authors.forename: Jay C
authors.initials: JC
authors.lastname: Easaw
authors.forename: Jenny
authors.initials: J
authors.lastname: Shannon
authors.forename: Fabyolla
authors.initials: F
authors.lastname: El-Tahche
authors.forename: Ian
authors.initials: I
authors.lastname: Walters
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Callaghan
mesh_terms: D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D011905:Genes, ras; D006801:Humans; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014227:Triazines; C509922:brivanib; D000409:Alanine; D000068818:Cetuximab
keywords: K-RAS; colorectal cancer; palliative chemotherapy; patient-reported outcomes; quality of life; questionnaires