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

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• 作者：Prof Winette TA van der Graaf ; MD^a ; ^{w.vandergraaf@onco.umcn.nl} ; Prof Jean-Yves Blay ; MD^b ; Sant P Chawla ; MD^c ; Dong-Wan Kim ; MD^d ; Binh Bui-Nguyen ; MD^e ; Paolo G Casali ; MD^f ; Prof Patrick Schö ; ffski ; MD^g ; Massimo Aglietta ; MD^h ; Arthur P Staddon ; MDⁱ ; Yasuo Beppu ; MD^j ; Axel Le Cesne ; MD^k ; Prof Hans Gelderblom ; MD^l ; Prof Ian R Judson ; MD^m ; Nobuhito Araki ; MDⁿ ; Monia Ouali ; MSc^o ; Sandrine Marreaud ; MD^o ; Rachel Hodge ; MSc^p ; Mohammed R Dewji ; MSc^p ; Corneel Coens ; MSc^o ; George D Demetri ; MD^q ; Prof Christopher D Fletcher ; MD^r ; Angelo Paolo Dei Tos ; MD^s ; Prof Peter Hohenberger ; MD^t ; on behalf of the EORTC Soft Tissue ; Bone Sarcoma Group ; the PALETTE study group
• 刊名：The Lancet
• 出版年：2012
• 出版时间：19-25 May, 2012
• 年：2012
• 卷：379
• 期：9829
• 页码：1879-1886
• 全文大小：291 K

文摘

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Summary

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 , number .

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.