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Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial
Winette T A van der Graaf1, Jean-Yves Blay, Sant P Chawla
1Radboud University Medical Centre, Department of Medical Oncology, Nijmegen, Netherlands. w.vandergraaf@onco.umcn.nl
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.
Insights
Pazopanib significantly improved progression-free survival in patients with metastatic non-adipocytic soft-tissue sarcoma. This multitargeted tyrosine kinase inhibitor offers a new treatment option after standard chemotherapy failure.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Pazopanib, a multitargeted tyrosine kinase inhibitor, demonstrates single-agent activity in advanced non-adipocytic soft-tissue sarcoma.
- Investigated the efficacy of pazopanib in metastatic non-adipocytic soft-tissue sarcoma post-standard chemotherapy failure.
Purpose of the Study:
- To evaluate the effect of pazopanib on progression-free survival (PFS) in patients with metastatic non-adipocytic soft-tissue sarcoma.
- To assess overall survival (OS) and safety profiles of pazopanib in this patient population.
Main Methods:
- Phase 3, randomized, double-blind, placebo-controlled study across 72 institutions in 13 countries.
- Angiogenesis inhibitor-naive patients with metastatic soft-tissue sarcoma progressing on chemotherapy were randomized (2:1) to pazopanib (800 mg daily) or placebo.
- Primary endpoint: PFS. Intention-to-treat efficacy analysis. ClinicalTrials.gov: NCT00753688.
Main Results:
- 369 patients randomized; 246 to pazopanib, 123 to placebo.
- Median PFS: 4.6 months (pazopanib) vs 1.6 months (placebo) (HR 0.31, p<0.0001).
- Median OS: 12.5 months (pazopanib) vs 10.7 months (placebo) (HR 0.86, p=0.25). Common adverse events included fatigue, diarrhea, nausea, weight loss, and hypertension.
Conclusions:
- Pazopanib demonstrates a significant improvement in PFS for patients with metastatic non-adipocytic soft-tissue sarcoma.
- Pazopanib represents a new therapeutic option for patients who have failed prior chemotherapy.
