PURPOSE
Pazopanib is an oral
angiogenesis inhibitor targeting
vascular endothelial growth factor receptor,
platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of
pazopanib monotherapy in treatment-naive and
cytokine-pretreated patients with advanced
renal cell carcinoma (RCC). PATIENTS AND METHODS Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral
pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival,
tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of
tumors were independently reviewed. Results Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were
cytokine pretreated (46%). PFS was significantly prolonged with
pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P < .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001), and the
cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001). The objective response rate was 30% with
pazopanib compared with 3% with placebo (P < .001). The median duration of response was longer than 1 year. The most common adverse events were
diarrhea,
hypertension, hair color changes,
nausea,
anorexia, and
vomiting. There was no evidence of clinically important differences in quality of life for
pazopanib versus placebo. CONCLUSION
Pazopanib demonstrated significant improvement in PFS and
tumor response compared with placebo in treatment-naive and
cytokine-pretreated patients with advanced and/or metastatic RCC.