Among patients with intermediate-risk metastatic clear cell renal cell carcinoma (ccRCC), nephrectomy after upfront pazopanib therapy is feasible and was associated with good outcomes, according to a study published in JAMA Oncology.1

The approval of numerous targeted agents has drastically changed the treatment landscape of metastatic RCC, leaving the role of cytoreductive nephrectomy uncertain. Researchers evaluated the safety and efficacy of neoadjuvant pazopanib therapy prior to cytoreductive nephrectomy in treatment-naive patients with metastatic ccRCC.

For the single-arm, phase 2 trial ( Identifier: NCT01512186), researchers enrolled 104 previously untreated patients with metastatic ccRCC to receive 12 to 14 weeks of upfront pazopanib treatment prior to undergoing planned cytoreductive nephrectomy and continued pazopanib following surgery. Patients were treated with pazopanib until disease progression or unacceptable toxicity.

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Results showed that 84% of the 100 evaluable patients achieved clinical benefit before cytoreductive nephrectomy. The median reduction in primary tumor size was 14.4%. No patients were unable to undergo surgery due to local disease progression.

Sixty-three patients (61%) underwent nephrectomy, with 14 patients (22%) reporting surgical complications. Thirteen patients did not undergo surgery as a result of progression of disease and 9 chose not to undergo surgery. One patient died after surgery.

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Median progression-free survival was 7.1 months (95% CI, 6.0-9.2) and median overall survival was 22.7 months (95% CI, 14.3-not estimable).

The findings suggest that upfront pazopanib therapy prior to nephrectomy may be beneficial for select patients with ccRCC. Further evaluation is warranted to determine the subpopulations that benefit most from this treatment strategy.


  1. Powles T, Sarwar N, Stockdale A, et al. Safety and efficacy of pazopanib therapy prior to planned nephrectomy in metastatic clear cell renal cancer. JAMA Oncol. 2016;2(10);1303-1309. doi: 10.1001/jamaoncol.2016.1197