Pazopanib in Patients with Metastatic Renal Cell Carcinoma Previously Treated with Sunitinib or Bevacizumab: A Sarah Cannon Research Institute Phase II Trial.

4659 Background: Pazopanib, a multi-targeted inhibitor of VEGFR, PDGFR, and c-KIT, is an active first-line agent in the treatment of advanced renal cell carcinoma (RCC). The efficacy of pazopanib in patients (pts) who have progressed on other anti-angiogenesis agents, particularly sunitinib, is unclear. METHODS Pts with metastatic clear-cell RCC who had progressed on or were intolerant of first-line single-agent sunitinib or bevacizumab were eligible. Additional criteria: ECOG PS 0 or 1; measurable disease (RECIST); previous nephrectomy unless clinically inappropriate; no active CNS metastases; adequate bone marrow, kidney, liver function; no risk factors for anti-angiogenesis agents; informed consent. All pts received pazopanib 800mg PO daily. Response was assessed every 8 weeks until progression. RESULTS 44 pts have been treated with pazopanib (previous sunitinib - 32; previous bevacizumab - 12). Additional pt characteristics: male/female, 77%/23%; Motzer risk low/intermediate/high, 25%/43%/32%; previous nephrectomy, 93%. The median duration of treatment was 24 weeks (range 0 to 52 weeks). After a median follow-up of 9 months, efficacy is as follows (see table). 37 pts remain alive, and 13 are continuing treatment. Toxicity with pazopanib was similar to previous reports: frequent grade 3/4 toxicity included fatigue (14%), hypertension (11%), proteinuria (11%). Three pts discontinued treatment due to toxicity, and 13 required dose reductions. CONCLUSIONS Pazopanib is active and well tolerated following treatment with either sunitinib or bevacizumab. [Table: see text].