About FDA


On October 19, 2009, the U. S. Food and Drug Administration granted approval to pazopanib tablets (VOTRIENT, GlaxoSmithKline) for the treatment of patients with advanced renal cell carcinoma.

The efficacy and safety of pazopanib were evaluated in an international, multicenter, randomized, double-blind trial comparing pazopanib to placebo.  All patients received best supportive care.  The trial was conducted in patients with metastatic renal cell carcinoma who were treatment naïve or who had received prior cytokine therapy.  Randomization was stratified according to performance status, prior nephrectomy, and prior cytokine therapy.

A total of 435 patients were randomized (2:1) to receive pazopanib (n=290) or placebo (n=145).  Demographics were balanced between the two arms.  Progression-free survival (PFS) was the trial’s primary endpoint.  The median PFS was 9.2 and 4.2 months in the pazopanib and placebo arms, respectively (HR = 0.46, p value < 0.001).  The effect was observed in both subgroups: treatment naïve (HR = 0.40) and cytokine pre-treated (HR = 0.54).  After documented radiological progression, patients receiving placebo could receive pazopanib.

The overall survival results are not mature; 40% of patients had died by the time of data cut-off.  The objective response rates were 30% and 3% for pazopanib and placebo, respectively. The median duration of responses was 13.5 months. 

The most common adverse reactions (≥20%) were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. Grade 3/4 adverse reactions that differed by ≥2% between arms were abnormal hepatic function, diarrhea, hypertension, and proteinuria.  QT prolongation has been seen with pazopanib.  Laboratory abnormalities occurring in >10% of patients and more commonly (>5%) in the pazopanib arm included increased transaminases, hyperglycemia, leukopenia, hyperbilirubinemia, neutropenia, hypophosphatemia, thrombocytopenia, lymphocytopenia, hyponatremia, hypomagnesemia, and hypoglycemia.  Deaths due to serious adverse events including cerebrovascular accident, gastric cancer, gastrointestinal hemorrhage, hemoptysis, bowel perforation, cardiac failure, myocardial infarction, hepatic failure and pneumonia occurred more commonly in the pazopanib arm.  Hepatic dysfunction is included as a boxed warning in the product label and two deaths were associated with hepatic failure.

Liver tests should be monitored every 4 weeks for at least the first 4 months with periodic monitoring thereafter.  Recommended dose modifications for pazopanib in patients with abnormal liver tests are included in the package insert. EKG and electrolytes should be monitored.

The recommended dose of pazopanib for treatment of advanced renal cell carcinoma is 800 mg, once daily at the same time without food (at least 1 hour before or 2 hours after a meal).

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf

Page Last Updated: 12/23/2015
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