title: Health utility of patients with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib: findings from GRID, a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo.
abstract: BACKGROUND
  In this analysis we report patients with advanced gastrointestinal stromal tumors (GIST) refractory to imatinib and sunitinib therapy as derived from the EuroQol-5D (EQ-5D) for progression-free (PF) and progressive disease health status.
  
  
  METHODS
  Data were analyzed from a phase III trial conducted at 57 hospitals in 17 countries (trial registration number, NCT01271712). Patients with advanced GIST were randomized (2:1) to receive blinded treatment using oral regorafenib 160 mg daily or placebo, plus best supportive care (BSC) in both groups, for the first 3 weeks of each 4-week cycle. EQ-5D-3L was administered on day 1 of each cycle before contact with their physician and before any study-related procedures. The effect of disease progression on the utility of EQ-5D was tested with paired-samples comparison and general linear mixed modeling (GLMM).
  
  
  RESULTS
  One hundred and eighty five patients [93 % of the intention-to-treat (ITT) population] completed 803 EQ-5D questionnaires: 77.7 % in progression-free (PF) state, 6.5 % at progression, 13.9 % following first progression, and 1.9 % after second progression. Mean baseline utility was 0.767 (SD 0.221) with no significant between-group differences for active treatment and BSC. The first post-progression health state was 0.647 (SD 0.343), suggesting significantly impaired health-related quality of life after confirmed disease progression showed a decrease of -0.120 (paired samples t test, p = 0.001). GLMM showed no effect of study treatment or cycle number on utility.
  
  
  CONCLUSIONS
  We demonstrate a significant and clinically meaningful difference in health state utility values between PF and progression. Utility values remained stable over successive regorafenib cycles after controlling for disease status and treatment type.
authors: Institute of Primary Care and Public Health, Cardiff University, Wales, UK.
authors: Chris D
authors: CD
authors: Poole
authors: Mark P
authors: MP
authors: Connolly
authors: Jane
authors: J
authors: Chang
authors: Craig J
authors: CJ
authors: Currie
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D015990:Placebo Effect; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage; D011788:Quality of Life; D000077210:Sunitinib; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; C559147:regorafenib; D000068877:Imatinib Mesylate; D000077210:Sunitinib