title: Q-TWiST analysis of panitumumab plus FOLFOX4 versus FOLFOX4 alone in patients with previously untreated wild-type RAS metastatic colorectal cancer.
abstract: BACKGROUND
  Panitumumab plus infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) significantly improved overall survival versus FOLFOX4 alone in patients with previously untreated wild-type RAS metastatic colorectal cancer (mCRC). We applied a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis to provide an integrated measure of clinical benefit, with the objective of comparing quality-adjusted survival between the two arms. We acknowledge that there are limitations associated with Q-TWIST methodology for crossover trials.
  
  
  METHODS
  For each treatment arm, the truncated mean times spent in the toxicity (TOX: grade 3 or 4 adverse events), time without symptoms of disease or toxicity (TWiST), and relapse (REL: after disease progression) states were estimated by the product-limit method, and adjusted using utility weights derived from patient-reported EuroQol 5-dimension measures. Sensitivity analyses were performed in which utility weights (varying from 0 to 1) were applied to time in the TOX and REL health states.
  
  
  RESULTS
  Quality-adjusted overall survival time was statistically significantly longer with panitumumab plus FOLFOX4 (20.5 months) than with FOLFOX4 alone (18.2 months) (P = 0.025).
  
  
  CONCLUSIONS
  In patients with previously untreated wild-type RAS mCRC, panitumumab plus FOLFOX4 significantly improved quality-adjusted survival compared with FOLFOX4 alone.
authors.affiliation: a a RTI Health Solutions , Research Triangle Park , NC , USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: b b Amgen GmbH , Zug , Switzerland.
authors.forename: Guy
authors.initials: G
authors.lastname: Hechmati
authors.affiliation: c c Amgen Inc. , Thousand Oaks , CA , USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.affiliation: c c Amgen Inc. , Thousand Oaks , CA , USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Maglinte
authors.affiliation: c c Amgen Inc. , Thousand Oaks , CA , USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Barber
authors.affiliation: d d ICO R. Gauducheau , St Herblain , France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077544:Panitumumab
chemical_list: D000911:Antibodies, Monoclonal; D009944:Organoplatinum Compounds; D000077544:Panitumumab; D002955:Leucovorin; D005472:Fluorouracil
keywords: Metastatic colorectal cancer; Panitumumab; Q-TWiST; Quality-adjusted survival