Journal Article

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

Casali, Paolo G, Fletcher, Christopher D, Blay, Jean-Yves, Judson, Ian R, Staddon, Arthur P, Le Cesne, Axel, Gelderblom, Hans, Marreaud, Sandrine, Dewji, Mohammed R, Coens, Corneel, Hohenberger, Peter, Araki, Nobuhito, Dei Tos, Angelo Paolo, Kim, Dong-Wan, Hodge, Rachel, Schöffski, Patrick, Aglietta, Massimo, Beppu, Yasuo, Ouali, Monia, van der Graaf, Winette TA, Chawla, Sant P, Bui-Nguyen, Binh, Demetri, George D

2012

Overview

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 with ClinicalTrials.gov, number NCT00753688. 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. Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy. GlaxoSmithKline.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Adolescent / Adult / Aged / angiogenesis / Antineoplastic Agents - therapeutic use / Biological and medical sciences / chemotherapy / Clinical medicine / Cross-Over Studies / Data collection / Dermatology / diarrhea / Disease-Free Survival / Double-Blind Method / Drug therapy / Female / General aspects / Growth factors / Heart attacks / Human health sciences / Humans / hypertension / Internal Medicine / Kaplan-Meier Estimate / Male / Medical sciences / metastasis / Middle Aged / Mortality / nausea / Oncologie / Oncology / patients / Pyrimidines - therapeutic use / Sarcoma / Sarcoma - drug therapy / Sarcoma - mortality / Sarcoma - secondary / Sciences de la santé humaine / Soft Tissue Neoplasms - drug therapy / Soft Tissue Neoplasms - mortality / Soft Tissue Neoplasms - secondary / Sulfonamides - therapeutic use / Treatment Outcome / Tumors / Tumors of the skin and soft tissue. Premalignant lesions / tyrosine / Vascular endothelial growth factor / weight loss / Wound healing / Young Adult