A Comprehensive Monograph on Pazopanib: Pharmacology, Clinical Efficacy, and Therapeutic Profile

I. Executive Summary

Pazopanib is an orally administered, second-generation, multi-targeted tyrosine kinase inhibitor (TKI) characterized by potent anti-angiogenic activity.[1] Developed by GlaxoSmithKline and now marketed by Novartis under the brand name Votrient®, it represents a significant therapeutic option in specific oncologic settings.[2] The primary mechanism of action involves the competitive inhibition of multiple receptor tyrosine kinases, most notably vascular endothelial growth factor receptors (VEGFR-1, -2, and -3), platelet-derived growth factor receptors (PDGFR-α and -β), and the stem cell factor receptor (c-Kit).[2] This blockade disrupts downstream signaling pathways crucial for angiogenesis, tumor cell growth, and metastasis.

Regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have granted marketing authorization for Pazopanib for the treatment of advanced Renal Cell Carcinoma (RCC) and for patients with advanced Soft Tissue Sarcoma (STS) who have received prior chemotherapy.[7] In RCC, its efficacy was established in a pivotal trial demonstrating a significant extension of progression-free survival (PFS) compared to placebo (median 9.2 vs. 4.2 months) and was later shown to be non-inferior to sunitinib, but with a more favorable quality-of-life profile.[11]