FDA OKs Drug for Soft-Tissue Sarcoma
WASHINGTON -- The FDA has approved the angiogenesis inhibitor pazopanib (Votrient) for treatment of advanced soft-tissue sarcoma that has progressed on chemotherapy.
The approval was based primarily on results of a pivotal phase III clinical trial that showed that patients with soft-tissue sarcoma treated with pazopanib had a threefold increase in progression-free survival compared with placebo.
"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," Richard Pazdur, MD, director of hematology and oncology products at the FDA, said in a statement.
"Drug development for sarcomas has been especially challenging because of the limited number of patients and multiple subtypes of sarcomas."
The FDA specifically excluded adipocytic sarcomas and gastrointestinal stromal tumors in approving the sarcoma indication, citing a lack of evidence to demonstrate efficacy.
Labeling for the drug includes a black-box warning about a potential for severe or fatal hepatotoxicity.
Additionally, physicians are instructed to monitor hepatic function in all patients treated with pazopanib and to discontinue the drug if laboratory results indicate liver dysfunction.
The phase III trial included 369 patients, representing almost two dozen subtypes of soft-tissue sarcoma.
The final results showed a median progression-free survival of 4.6 months in the pazopanib arm and 1.6 months in the placebo arm, which corresponded to a 65% reduction in the hazard for progression (HR 0.35, P <0.001)
The results also showed a nonsignificant trend toward improved overall survival in the pazopanib arm (12.6 versus 10.7 months, HR 0.87, P =0.256).
The most frequent adverse effects associated with pazopanib were fatigue, diarrhea, nausea, vomiting, weight loss, hypertension, decreased appetite, headache, altered taste, dyspnea, and skin discoloration.