title: Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial.
abstract: BACKGROUND
  Pazopanib, a multitargeted tyrosine kinase inhibitor, has single-agent activity in patients with advanced non-adipocytic soft-tissue sarcoma. We investigated the effect of pazopanib on progression-free survival in patients with metastatic non-adipocytic soft-tissue sarcoma after failure of standard chemotherapy.
  
  
  METHODS
  This phase 3 study was done in 72 institutions, across 13 countries. Patients with angiogenesis inhibitor-naive, metastatic soft-tissue sarcoma, progressing despite previous standard chemotherapy, were randomly assigned by an interactive voice randomisation system in a 2:1 ratio in permuted blocks (with block sizes of six) to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Patients, investigators who gave the treatment, those assessing outcomes, and those who did the analysis were masked to the allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00753688.
  
  
  RESULTS
  372 patients were registered and 369 were randomly assigned to receive pazopanib (n=246) or placebo (n=123). Median progression-free survival was 4·6 months (95% CI 3·7-4·8) for pazopanib compared with 1·6 months (0·9-1·8) for placebo (hazard ratio [HR] 0·31, 95% CI 0·24-0·40; p<0·0001). Overall survival was 12·5 months (10·6-14·8) with pazopanib versus 10·7 months (8·7-12·8) with placebo (HR 0·86, 0·67-1·11; p=0·25). The most common adverse events were fatigue (60 in the placebo group [49%] vs 155 in the pazopanib group [65%]), diarrhoea (20 [16%] vs 138 [58%]), nausea (34 [28%] vs 129 [54%]), weight loss (25 [20%] vs 115 [48%]), and hypertension (8 [7%] vs 99 [41%]). The median relative dose intensity was 100% for placebo and 96% for pazopanib.
  
  
  CONCLUSIONS
  Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy.
  
  
  BACKGROUND
  GlaxoSmithKline.
authors.affiliation: Radboud University Medical Centre, Department of Medical Oncology, Nijmegen, Netherlands. w.vandergraaf@onco.umcn.nl
authors.forename: Winette T A
authors.initials: WT
authors.lastname: van der Graaf
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Sant P
authors.initials: SP
authors.lastname: Chawla
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.forename: Binh
authors.initials: B
authors.lastname: Bui-Nguyen
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Casali
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Staddon
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Beppu
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Ian R
authors.initials: IR
authors.lastname: Judson
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Araki
authors.forename: Monia
authors.initials: M
authors.lastname: Ouali
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marreaud
authors.forename: Rachel
authors.initials: R
authors.lastname: Hodge
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Dewji
authors.forename: Corneel
authors.initials: C
authors.lastname: Coens
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Fletcher
authors.forename: Angelo Paolo
authors.initials: AP
authors.lastname: Dei Tos
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007191:Indazoles; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib