According to results of the PALETTE trial, treatment with pazopanib increased progression-free survival (PFS) almost three fold among patients with metastatic soft-tissue sarcoma whose disease had progressed following chemotherapy. The results are published Online First in The Lancet.

In the United States, an estimated 11,000 individuals are diagnosed with soft-tissue sarcomas each year – accounting for just 1% of all adult cancers. However, progress in developing new effective treatments for the disease has been slow during the last three decades. Median overall survival is approximately 12 months for patients with advanced stages of the disease.

Pazopanib has been approved for the treatment of kidney cancer. The drug targets platelet-derived growth factor receptors (PDGF) and all three vascular endothelial growth factor (VEGF) receptors that play a role in growing new blood vessels (angiogenesis).

In the PALETTE study, 369 patients with metastatic soft-tissue sarcoma whose disease had progressed after chemotherapy were enrolled from 72 institutions across 13 countries to participate in the study. Individuals with liposarcomas and gastro-intestinal stromal tumors (GIST) were not included in the study.

The study was conducted by Winette van der Graaf from Radboud University Nijmegen Medical Center, Netherlands and colleagues from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group, and other cancer centers worldwide.

The researchers randomly assigned 246 patients to receive oral pazopanib and 123 to receive placebo. At a median follow-up of 15 months, the team found that PFS improved by 3 months for participants receiving pazopanib (4-6 months) vs. 1.6 months for patients given placebo. However, overall survival between the two groups was not significantly different – 12.5 months in the pazopanib group vs. 10.7 in the placebo group.

Adverse effects of pazopanib included:

34 (14%) patients stopped taking pazopanib due to toxic effects associated to the drug. Of the 8 deaths in the pazopanib group, one was due to multi-organ failure that may have been associated to the drug.

Between the two groups, self-reported quality of life did not differ considerably. However, the team found that fatigue, nausea and diarrhea were significantly worse among patients in the pazopanib group.

The researchers conclude:

“Progression-free survival improved in patients of all ages and for most histological subgroups. Pazopanib is the first active oral agent for patients with soft-tissue sarcomas, excluding liposarcomas and GIST, and is a new treatment option for patients with this rare group of tumors.”

In an associated comment, Vivien Bramwell from the Tom Baker Cancer Center, Calgary, Canada, explained:

“This was a well-designed and conducted study, that showed a 3 month improvement in the primary outcome of progression-free survival. [But] the desired effect of palliative chemotherapy is that tumor shrinkage or delay of progression will improve patients’ activity or well-being, but this effect was not definitively shown.

The investigators conclude that pazopanib provides a new treatment option, and there will be demand for it, but will funding agencies be willing to, or able to, pay?”

Written By Grace Rattue