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U.S. Department of Health and Human Services

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Pazopanib

On April 26, 2012, the U. S. Food and Drug Administration approved pazopanib tablets (VOTRIENT, a registered Trademark of GlaxoSmithKline) for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. The efficacy of pazopanib for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors (GIST) has not been demonstrated.

The approval is based on a randomized, double-blind, placebo-controlled, multicenter trial in patients with metastatic STS who had received prior chemotherapy, including an anthracycline. 

The trial enrolled 369 patients who were randomly allocated (2:1) to receive pazopanib 800 mg orally once daily (N=246) or placebo (N=123). Treatment continued until disease progression, unacceptable toxicity, and/or consent withdrawal. The majority of patients were female (59%), and the median age was 55.Forty-three percent of patients had leiomyosarcoma, 10% had synovial sarcoma, and 47% had other soft tissue sarcomas. Fifty-six percent had received 2 or more prior systemic therapies. The median treatment duration was 4.5 and 1.9 months for patients on the pazopanib and placebo arms, respectively.

A statistically significant improvement in progression-free survival (PFS) in patients receiving pazopanib compared to those receiving placebo was demonstrated [HR 0.35 (95% CI: 0.26, 0.48; p< 0.001, log-rank test)]. The median PFS was 4.6 and 1.6 months for patients on the pazopanib and placebo arms, respectively. The PFS improvement in the 3 pre-specified histological subgroups of leiomyosarcoma (HR=0.37; 95% CI: 0.23, 0.60), synovial sarcoma (HR=0.43; 95% CI: 0.19, 0.98) and other soft tissue sarcomas (HR=0.39; 95% CI: 0.25, 0.60) was consistent with the PFS improvement in the overall population.

The objective response rate was 4% for patients receiving pazopanib; no patient in the placebo arm was noted to have a response. At the protocol-specified final analysis of overall survival, the median survival was 12.6 and 10.7 months for patients on the pazopanib and placebo arms, respectively (HR=0.87; 95% CI: 0.67, 1.12).

The most common (≥20%) adverse reactions in STS patients treated with pazopanib were fatigue, diarrhea, nausea, weight loss, hypertension, decreased appetite, vomiting, tumor pain, hair color changes, musculoskeletal pain, headache, dysgeusia, dyspnea and skin hypopigmentation. Other significant adverse reactions reported in pazopanib-treated STS patients included hepatic toxicity, arterial and venous thrombotic events, hemorrhage, gastrointestinal perforation and fistula formation, pneumothorax and left ventricular dysfunction.

The recommended dose and schedule of pazopanib is 800 mg orally once daily, administered without food (at least 1 hour before or 2 hours after a meal).

Full prescribing information, including Boxed Warning for severe and fatal hepatotoxicity, clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022465s-010S-012lbl.pdf

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).