Pazopanib: a Review in Advanced Renal Cell Carcinoma

• Published in: Targeted oncology 2017-08, Vol.12 (4), p.543-554
• Main Author: Frampton, James E.
• Format: Article
• Language: English
• Subjects: Adis Drug Evaluation; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Biomedicine; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Clinical trials; Female; Growth factors; Health risk assessment; Humans; Inhibitor drugs; Kidney cancer; Male; Medicine; Medicine & Public Health; Metastasis; Oncology; Pyrimidines - administration & dosage; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Sulfonamides - administration & dosage; Sulfonamides - pharmacology; Sulfonamides - therapeutic use; Targeted cancer therapy
• ISSN: 1776-2596; 1776-260X
• DOI: 10.1007/s11523-017-0511-8

Pazopanib (Votrient®), an orally administered multi-targeted tyrosine kinase inhibitor that predominantly inhibits vascular endothelial growth factor receptor-1, −2 and −3, platelet-derived growth factor receptor-α and -β, and the stem cell factor receptor c-Kit, is approved in the EU, the USA and other countries for the treatment of advanced renal cell carcinoma (RCC). In randomized controlled trials in patients with advanced, predominantly clear-cell RCC, pazopanib significantly improved progression-free survival (PFS) compared with placebo in both treatment-naïve and cytokine-pretreated patients and, as a first-line therapy, was noninferior to intermittent sunitinib with respect to PFS. However, pazopanib had a tolerability profile that was distinguishable from that of sunitinib, based on lower incidences of most adverse events, particularly those associated with discomfort, such as fatigue, hand-foot syndrome and stomatitis. Consistent with this, health-related quality of life (HR-QOL) measures evaluating fatigue, hand/foot soreness and mouth/throat soreness significantly favoured pazopanib over sunitinib. In addition, significantly more patients expressed a preference for pazopanib over sunitinib, primarily because of better overall HR-QOL and less fatigue. Efficacy and tolerability findings from these prospective clinical trials have been substantiated by evidence from a number of retrospective studies evaluating unselected real-world patients with metastatic RCC who received pazopanib (or sunitinib) as a first-line therapy. Thus, data from clinical trials supplemented with that from clinical practice support the use of pazopanib as a standard or alternative first-line treatment for advanced or metastatic RCC.