Pre-Nephrectomy Pazopanib ‘Feasible’ In Metastatic Clear-Cell RCC

Upfront targeted therapy could delay cytoreductive nephrectomy in selected patients with metastatic clear-cell renal cell carcinoma

medwireNews: Upfront treatment with the tyrosine kinase inhibitor (TKI) pazopanib prior to undergoing cytoreductive nephrectomy may be an option for certain newly diagnosed patients with metastatic clear-cell renal cell carcinoma (RCC), study findings indicate.

Such an approach is “feasible” in patients with intermediate-risk disease, as per the Memorial Sloan Kettering Cancer Center criteria, say the study authors. But they question the role of cytoreductive nephrectomy in poor-risk patients, who had poor outcomes irrespective of whether they underwent surgery.

The researchers explain that the sequence of the current standard of care – nephrectomy followed by targeted therapy – has not been evaluated in the TKI era, and that a potential problem could be the delay in administering systemic treatment. Thus, they evaluated the alternative approach of giving a TKI ahead of surgery.

Of 104 treatment-naïve patients given pazopanib 800 mg/day until a minimum of 48 hours before surgery for a median duration of 13 weeks, 100 were assessable for clinical benefit, which was defined as no clinical or radiological progression at the time of nephrectomy.

The phase II trial achieved its primary objective, as 84% of participants achieved clinical benefit, which was greater than the predefined limit of 75%, reports the team led by Thomas Powles, from Queen Mary University of London in the UK.

Median progression-free survival (PFS) and overall survival (OS) in the total study population were 7.1 months and 22.7 months, respectively. But participants who did not achieve clinical benefit had a worse OS compared with those who did, at a median of 3.9 versus 24.0 months. Outcomes were also poor for the 18% of patients with poor-risk disease – nearly half (39%) had disease progression as best response prior to surgery and median PFS and OS were a respective 3.9 and 5.7 months.

Sixty-three percent of the 104 accrued patients underwent nephrectomy. Surgical complications occurred in 22% of nephrectomies, with bleeding (8%) and delayed wound healing (6%) the most common problems. Surgery-related mortality was low, at 2%.

Although the researchers believe that this clinical approach is “potentially attractive” for selected patients, they urge caution given the “areas of concern”.

Specifically, 39% of patients did not undergo nephrectomy, mainly as a result of disease progression before surgery, patient choice and inadequate fitness for surgery. This percentage is higher than the figures for nephrectomy before systemic treatment, say the authors.

Furthermore, a small proportion did not have surgery owing to the development of morbidity. “This group of patients is a concern because nephrectomy prior to pazopanib therapy may have been possible and may have improved outcome”, the team writes in JAMA Oncology.


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; Advance online publication 2 June. doi: 10.1001/jamaoncol.2016.1197

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