TY - JOUR
T1 - Pazopanib for metastatic soft-tissue sarcoma (PALETTE)
T2 - A randomised, double-blind, placebo-controlled phase 3 trial
AU - Van Der Graaf, Winette T.A.
AU - Blay, Jean Yves
AU - Chawla, Sant P.
AU - Kim, Dong Wan
AU - Bui-Nguyen, Binh
AU - Casali, Paolo G.
AU - Schöffski, Patrick
AU - Aglietta, Massimo
AU - Staddon, Arthur P.
AU - Beppu, Yasuo
AU - Le Cesne, Axel
AU - Gelderblom, Hans
AU - Judson, Ian R.
AU - Araki, Nobuhito
AU - Ouali, Monia
AU - Marreaud, Sandrine
AU - Hodge, Rachel
AU - Dewji, Mohammed R.
AU - Coens, Corneel
AU - Demetri, George D.
AU - Fletcher, Christopher D.
AU - Dei Tos, Angelo Paolo
AU - Hohenberger, Peter
N1 - Funding Information:
This study was sponsored by GlaxoSmithKline. We thank EORTC Headquarters, the GlaxoSmithKline study team, and all investigators, patients, and their families, for their contributions to this study. This article was reviewed and approved by all authors.
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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 inhibitornaive,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.
AB - 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 inhibitornaive,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.
UR - http://www.scopus.com/inward/record.url?scp=84861098484&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(12)60651-5
DO - 10.1016/S0140-6736(12)60651-5
M3 - Article
C2 - 22595799
AN - SCOPUS:84861098484
SN - 0140-6736
VL - 379
SP - 1879
EP - 1886
JO - The Lancet
JF - The Lancet
IS - 9829
ER -