Relationships between pazopanib exposure and clinical safety and efficacy in patients with advanced renal cell carcinoma

Background: Pazopanib, an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-Kit, is approved in locally advanced/metastatic renal cell carcinoma (RCC). Methods: Data from trials in advanced solid tumours and advanced/metastatic RCC were used to explore the relationships between plasma pazopanib concentrations and biomarker changes, safety, and efficacy. Initially, the relationships between pharmacokinetic parameters and increased blood pressure were investigated, followed by analysis of steady-state trough concentration ( C τ) and sVEGFR2, safety, progression-free survival (PFS), response rate, and tumour shrinkage. Efficacy/safety end points were compared at C τ decile boundaries. Results: Strong correlation between increased blood pressure and C τ was observed ( r 2 =0.91), whereas weak correlation was observed between C τ and decline from baseline in sVEGFR2 ( r 2 =0.27). C τ threshold of >20.5 μ g ml −1 was associated with improved efficacy (PFS, P