Pazopanib prolongs progression-free survival in patients with advanced soft-tissue Sarcoma

by Bruce Sylvester – Emerging uses of FDA Approved Drugs –

Treatment with pazopanib nearly tripled progression-free survival (PFS), compared with placebo, among patients with metastatic soft-tissue sarcoma whose disease has progressed following standard chemotherapy.

This is the first randomized, phase 3 trial in metastatic soft-tissue sarcoma to show improvement in PFS.

“Progression-free survival improved in patients of all ages and for most histological subgroups,” the authors wrote. “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 tumours.”

The findings appeared on May 16 online in The Lancet.

Pazopanib targets platelet-derived growth factor receptors (PDGF) and all 3 vascular endothelial growth factor (VEGF) receptors involved in angiogenesis. It is FDA-approved to treat kidney cancer.
In the PALETTE study, Winette van der Graaf, MD, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands, and enrolled 369 patients with metastatic soft-tissue sarcoma whose disease had progressed after chemotherapy. A total of  72 institutions in 13 countries participated in the study

Patients with gastro-intestinal stromal tumours (GIST) and liposarcomas were excluded.

The subjects were randomized to oral pazopanib (n = 246) or placebo (n = 123).

For a median follow-up of 15 months, the investigators reported progression-free survival of 4.6 months for subjects  receiving pazopanib versus 1.6 months for subjects receiving placebo.

But there was no significant gain in overall survival (12.5 months vs 10.7 months) in patients receiving pazopanib.

Common side effects of pazopanib were fatigue, diarrhoea, hypertension, nausea, and weight loss. Newly reported side effects were venous thromboembolic events, pneumothorax, and cardiotoxicity.

Pazopanib was discontinued in 34 (14%) patients because of toxic effects related to the drug. Of 8 fatal adverse events in the pazopanib group, 1 was multi-organ failure that might have been related to the study drug.

In an accompanying comment, Vivien Bramwell, MD, Tom Baker Cancer Centre, Calgary, Alberta, wrote: “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 tumour 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?”