Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial

Lancet. 2012 May 19;379(9829):1879-86. doi: 10.1016/S0140-6736(12)60651-5. Epub 2012 May 16.

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.

Findings: 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.

Interpretation: Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy.

Funding: GlaxoSmithKline.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Cross-Over Studies
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pyrimidines / therapeutic use*
  • Sarcoma / drug therapy*
  • Sarcoma / mortality
  • Sarcoma / secondary
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / mortality
  • Soft Tissue Neoplasms / secondary
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Pyrimidines
  • Sulfonamides
  • pazopanib

Associated data

  • ClinicalTrials.gov/NCT00753688