Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma

Thomas E Hutson, Ian D Davis, Jean-Pascal H Machiels, Paul L De Souza, Sylvie Rottey, Bao-Fa Hong, Richard J Epstein, Katherine L Baker, Lauren McCann, Theresa Crofts, Lini Pandite, Robert A Figlin
Journal of Clinical Oncology 2010 January 20, 28 (3): 475-80

PURPOSE: Inactivation of the von Hippel-Lindau gene in clear-cell renal cell carcinomas (RCC) leads to overexpression of hypoxia inducible factor, a transcription factor regulating vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) gene expression. Pazopanib, an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor, and c-KIT, was evaluated in patients with RCC.

PATIENTS AND METHODS: This phase II study was designed as a randomized discontinuation study but was revised to an open-label study on the recommendation of the data monitoring committee (based on week 12 response rate [RR] of 38% in the first 60 patients). The primary end point was changed from progressive disease rate at 16 weeks postrandomization to RR. Pazopanib 800 mg was administered orally once daily. Pazopanib 800 mg was administered orally once daily.

RESULTS: The study enrolled 225 patients with metastatic RCC; 155 patients (69%) were treatment naïve, and 70 patients (31%) had received one prior cytokine- or bevacizumab-containing regimen. Overall RR was 35%; median duration of response was 68 weeks. Median progression-free survival (PFS) was 52 weeks. Eastern Cooperative Oncology Group performance status of 0 and time from diagnosis to treatment of more than 1 year were correlated with prolonged PFS. Pazopanib was generally well tolerated. The most common adverse events were diarrhea, fatigue, and hair depigmentation. The most common laboratory abnormalities were elevated AST and ALT.

CONCLUSION: Pazopanib demonstrated durable activity in patients with advanced RCC and was generally well tolerated in this population. These findings support the further development of pazopanib in advanced RCC.

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