Targeted therapy with pazopanib prolongs progression free survival in advanced soft-tissue sarcoma (The Lancet)

For patients with advanced soft-tissue sarcoma whose disease has progressed following standard chemotherapy, treatment with pazopanib nearly tripled progression free survival (PFS) compared with placebo, according to the results of the PALETTE trial, published Online First in The Lancet. This is the first time a randomized phase 3 trial of advanced and metastatic soft tissue sarcoma has shown improvement in PFS.

Soft tissue sarcomas are relatively rare and account for just 1% of all adult cancers, with the annual number of new cases in the USA estimated at 11 000. In the last 30 years there has been little progress in developing effective treatments. There are many subgroups of soft tissue sarcomas. In advanced stages, median overall survival is about 12 months. Recent research has shown that pazopanib (a drug that targets the growth of new cancer-related blood-vessels) has promising activity in patients with soft tissue sarcomas.

Pazopanib is a drug that targets all three vascular endothelial growth factor (VEGF) receptors involved in angiogenesis and has been approved to treat kidney cancer.

In this study, Winette van der Graaf from Radboud University Nijmegen Medical Centre, Netherlands and colleagues from the European Organisation Of Research and Treatment of Cancer Soft Tissue and Bone Sarcoma group, and other cancer center worldwide enrolled 369 patients with advanced soft-tissue sarcoma whose disease had progressed after chemotherapy. In total 72 institutions across 13 countries participated in the study. Patients were randomly assigned to oral pazopanib (246 patients) or placebo (123).

Results showed that the time it took for a patient’s disease to progress was improved by 3 months for those receiving pazopanib (4.6 months) compared with those given placebo (1.6 months) at median 15 months follow-up. However, patients receiving pazopanib did not live significantly longer (12.5 months vs. 10.7 months).

Dr. van der Graaf remarks: “Finally, a new and oral drug is available for patients with soft tissue sarcomas. This is an important step forward and opens the way towards new clinical studies. We have shown again that even in rare tumors such as soft tissue sarcomas, we can do a study in a collaborative spirit in a very short period of time.”

Common side effects of pazopanib included fatigue, diarrhea, hypertension, nausea, and weight loss. As compared to the registration of pazopanib in renal cell cancer newly reported side effects were venous thromboembolic events, pneumothorax, and cardio toxicity.

Treatment dose was lowered in 34(14%) patients because of toxic effects related to the drug. Of eight fatal adverse events in the pazopanib group, one was multiorgan failure that might have been related to the study drug. Overall, self-reported quality of life did not differ significantly between the placebo and pazopanib groups, but individual components such as diarrhea, nausea, and fatigue were significantly worse on pazopanib.

The authors conclude: “Progression-free survival improved in patients of all ages and for most histological subgroups. Patients with adipocytic soft tissue sarcomas were not part of this study …Pazopanib is the first active oral agent for patients with non-gastrointestinal stromal soft-tissue sarcomas, and is a new treatment option for patients with this rare group of tumors.”

In an accompanying “Comment”, Vivien Bramwell from the Tom Baker Cancer Centre, Calgary, Canada says: “The desired effect of palliative chemotherapy is that tumor shrinkage or delay of progression will improve patient function or well-being, but this was not definitively demonstrated.”

She adds: “The authors conclude that pazopanib provides a new treatment option, and there will be demand, but will funding agencies be willing to pay?”

About the EORTC

The EORTC is a unique organization – a vibrant example of the fact that academic science and research know no national boundaries. Established in 1962, the EORTC is a non-profit European research organization operating as an international association under Belgian law.

The EORTC currently links a network of more than 2,500 pre-clinical scientists and oncologists in more than 300 hospitals in over 30 countries. It encompasses all aspects of cancer research, from translational research and new drug development to large phase III clinical trials and meta-analyses.

The 170 members of the EORTC Headquarters staff handle some 6,000 new patients enrolled each year in cancer clinical trials, approximately 30 protocols that are permanently open to patient entry, over 50,000 patients who are in follow-up, and a database of more than 180,000 patients.

The ultimate goal of the EORTC is to improve the future of cancer therapy by developing new agents and innovative approaches and to test more effective treatment strategies using commercially available drugs, or surgery and radiotherapy.

http://www.eortc.org/

For full Article and Comment see:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract

John Bean