title: Quality-adjusted time without symptoms or toxicity analysis of pazopanib versus sunitinib in patients with renal cell carcinoma.
abstract: BACKGROUND
  In a phase 3, randomized, open-label trial (Pazopanib versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma, COMPARZ; NCT00720941), pazopanib was found to be noninferior to sunitinib in terms of progression-free survival in patients with metastatic renal cell carcinoma with no prior therapy. Overall treatment differences were evaluated in a post hoc analysis with a quality-adjusted time without symptoms or toxicity (Q-TWiST) methodology.
  
  
  METHODS
  Each patient's overall survival was partitioned into 3 mutually exclusive health states: time with grade 3 or 4 toxicity (TOX), time without symptoms of disease or grade 3/4 toxicity of treatment, and time after tumor progression or relapse (REL). The time spent in each state was weighted by a health-state utility associated with that state and summed to calculate the Q-TWiST. A threshold utility analysis was used, and utilities were applied across the range of 0 (similar to death) to 1 (perfect health).
  
  
  RESULTS
  A total of 1110 patients were enrolled (557 on pazopanib and 553 on sunitinib). The mean TOX was 31 days (95% confidence interval, 13-48 days) longer for sunitinib versus pazopanib. In the threshold utility analysis, the difference in the Q-TWiST ranged from -11 days (utility for TOX, 1; utility for REL, 0) to 43 days (utility for TOX, 0; utility for REL, 1) in favor of pazopanib across most utility combinations. Differences were significant in less than half of the utility combinations examined, and this typically occurred when the utility for TOX was lower than the utility for REL.
  
  
  CONCLUSIONS
  Patients randomized to pazopanib had a slightly longer Q-TWiST in comparison with sunitinib patients, and this was primarily due to the reduced length of TOX.
authors.affiliation: Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Beaumont
authors.affiliation: Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, North Carolina.|Comprehensive Cancer Center at Wake Forest Baptist, Winston-Salem, North Carolina.
authors.forename: John M
authors.initials: JM
authors.lastname: Salsman
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Jose
authors.initials: J
authors.lastname: Diaz
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania.
authors.forename: Keith C
authors.initials: KC
authors.lastname: Deen
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania.
authors.forename: Lauren
authors.initials: L
authors.lastname: McCann
authors.affiliation: Barts Cancer Institute, London, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
authors.affiliation: Novartis Pharma Services AG, Basel, Switzerland.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Hackshaw
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.affiliation: Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.
authors.forename: David
authors.initials: D
authors.lastname: Cella
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects*; D011788:Quality of Life; D013449:Sulfonamides / Q000009:adverse effects*; D000077210:Sunitinib; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C516667:pazopanib; D000077210:Sunitinib
keywords: angiogenesis inhibitors; drug toxicity; pazopanib; renal cell carcinomas; sunitinib