The FDA has approved pazopanib (Votrient, GlaxoSmithKline) for the treatment of patients with advanced soft tissue sarcoma who have previously received chemotherapy.
Pazopanib is an oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR), a series of proteins that promote angiogenesis, the formation of blood vessels in tumors.
The approval was expected after the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 11 to 2 in favor of recommending the approval of the drug in March.
Soft tissue sarcoma is a rare cancer with several subtypes. Surgery can usually be used to cure patients with lower-grade tumors, but patients with higher-grade tumors often experience local treatment failure and an increased risk of developing metastatic disease.
The National Cancer Institute estimates that 11,280 new cases of adult soft tissue sarcoma are expected to be diagnosed in 2012, with 3900 patients dying from the disease.
“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,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement regarding pazopanib’s approval. “Drug development for sarcomas has been especially challenging because of the limited number of patients and multiple subtypes of sarcomas.”
The results of a phase III clinical trial, VEG110727, factored heavily in this latest approval of pazopanib. In that trial, 369 patients with advanced soft tissue sarcoma who were previously treated with chemotherapy were selected to receive either pazopanib (n=246) or a placebo (n=123). Patients in the pazopanib arm had significantly higher progression-free survival (PFS) compared with patients in the placebo arm. PFS in the pazopanib arm was 4.6 months, compared with 1.6 months in the placebo arm, with a hazard ratio (HR) of 0.35 (95% CI, .26-.48; P <.001).
However, the drug’s recommendation status and value have been debated, based on the lack of improvement in overall survival (OS) in patients who received pazopanib. In the final analysis, median OS in the pazopanib arm was 12.6 months (95% CI, 10.9-14.9) compared with 10.7 months in the placebo arm (95% CI, 9.0, 13.1) with a HR of 0.87 (95% CI, 0.67-1.12; P
Additionally, a number of serious adverse events were linked to pazopanib. A total of 34 patients (14%) in the pazopanib arm discontinued the drug due to toxicity, compared to one patient (1%) in the placebo arm. The most common drug-related toxicities that caused patients to discontinue the drug were liver toxicity, hemorrhagic events, hypertension, proteinuria, and myocardial dysfunction.
In October 2009, pazopanib was approved to treat patients with renal cell carcinoma. In the approval for soft tissue carcinoma, the label states that the drug is not approved for patients with gastrointestinal stromal tumors (GIST) or adipocytic soft tissue carcinoma.