"Soft tissue sarcomas are a diverse group of tumors and the approval of Votrient for this general class of tumors is the first in decades," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research said in the FDA statement. He noted that drug development for sarcomas "has been especially challenging because of the limited number of patients and multiple subtypes of sarcomas."
Approval was based on the phase III PALETTE study of 369 patients with more than 20 subtypes of advanced soft tissue sarcomas who had received prior chemotherapy. Progression-free survival reached a median of 4.6 months among those randomized to treatment with pazopanib, compared with a median of 1.6 months among those randomized to placebo, a 65% reduced risk that was a statistically significant difference.
Soft tissue sarcoma, which has many subtypes, is diagnosed in about 10,000 people every year in the United States, according to the FDA. The drug received orphan drug status for this indication. It is not approved for patients with adipocytic soft tissue sarcoma and gastrointestinal stromal tumors (GIST).
Pazopanib, a tyrosine kinase inhibitor taken orally, targets the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and stem cell growth factor. It was initially approved in October 2009 for the treatment of advanced renal cell carcinoma.
The approval comes about a month after the FDA’s Oncologic Drugs Advisory Committee voted 11-2 that the pazopanib had a favorable risk-benefit profile as a treatment for advanced soft-tissue sarcomas, in patients who have received prior chemotherapy. Panelists said that while the effects of drug were marginal, they believed the effect was real and that a benefit of a few months was meaningful to patients, especially with few treatment options available.
The most common side effects in pazopanib-treated patients included fatigue, diarrhea, nausea, weight loss, hypertension, decreased appetite, vomiting, tumor and muscle pain, hair color changes, headache, a distorted sense of taste, shortness of breath, and skin discoloration.
The pazopanib label has a boxed warning about the potential for hepatotoxicity with treatment, which can be fatal, and the need to monitor hepatic function in patients treated with the drug.
Pazopanib is marketed by GlaxoSmithKline.