Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial
Mené sur 369 patients atteints d'un sarcome avancé non adipocytaire des tissus mous, cet essai de phase III évalue, du point de vue de la survie sans progression, le pazopanib après l'échec d'une chimiothérapie standard
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. 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 withClinicalTrials.gov, numberNCT00753688. 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%]vs155 in the pazopanib group [65%]), diarrhoea (20 [16%]vs138 [58%]), nausea (34 [28%]vs129 [54%]), weight loss (25 [20%]vs115 [48%]), and hypertension (8 [7%]vs99 [41%]). The median relative dose intensity was 100% for placebo and 96% for pazopanib. Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy. GlaxoSmithKline.
The Lancet , résumé, 2011