Mechanism of Action

Votrient (pazopanib) is a vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor that acts at all three isoforms: VEGFR-1, VEGFR-2 and VEGFR-3. VEGF is a chemical signal produced by cells that stimulates the growth of new blood vessels. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate. When VEGF is overexpressed, it can contribute to disease. Solid cancers need an adequate blood supply or they will not be able to grow. Hence, cancer that can express VEGF is able to grow and metastasize.

Side Effects

Adverse events associated with the use of Votrient for RCC may include, but are not limited to, the following:

Diarrhea

Hypertension

Hair color change

Nausea

Fatigue

Anorexia

Vomiting

Adverse reactions associated with the use of Votrient for STS may include, but are not limited to, the following:

Fatigue

Diarrhea

Nausea

Decreased weight

Hypertension

Decreased appetite

Vomiting

Tumor pain

Hair color changes

Musculoskeletal pain

Headache

Dysgeusia

Dyspnea

Skin hypopigmentation

Dosing/Administration

Votrient is supplied as a tablet designed for oral administration. The recommended initial dose is 800 mg orally once daily without food (at least one hour before or two hours after a meal). The dose of Votrient should not exceed 800 mg.

Clinical Trial Results

RCC: The FDA approval of Votrient was based on the results of a randomized, double-blind, placebo-controlled, multicenter study in 435 subjects with locally advanced and/or metastatic RCC who had received either no prior therapy or one prior cytokine-based systemic therapy. The subjects were randomized to receive Votrient 800 mg once daily or placebo once daily. The primary objective progression-free survival (PFS); the secondary end points included overall survival (OS), overall response rate (RR) and duration of response. The median progression free survival for the overall population was 9.2 months in the Votrient arm versus 4.2 months in the placebo group (P<0.001). The median progression free survival for the treatment-naïve subgroup was 11.1 months versus 2.8 months and in the Cytokine pretreated subgroup 7.4 months versus 4.2 months. In the Votrient arm, there was a 30 percent response rate (complete response + partial response) versus 3 percent in the placebo arm. The median duration of response was 58.7 weeks in the Votrient arm.

STS: The FDA approval of Votrient was based on the results of a randomized, double-blind, placebo-controlled, multicenter trial named PALETTE. The study enrolled 369 subjects with STS who did not respond to previous chemotherapy treatment or who were ineligible for chemotherapy treatment. Subjects with adipocytic STS or gastrointestinal stromal tumors were excluded from the trial. Subjects were randomized 2:1 to be treated with Viotrent 800 mg per day or placebo. The primary efficacy end point was the rate of progression-free survival (PFS) and was assessed by independent radiological review. Secondary efficacy end points included overall survival (OS), overall response rate and duration of response. The median duration of PFS among the Votrient arm was 4.6 months against 1.6 months in the placebo arm. The overall response rate in the treatment group was 4 percent for nine months compared to 0 percent in the placebo group.