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Original Investigation
December 13, 2018

Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib: The SURTIME Randomized Clinical Trial

Author Affiliations
  • 1The Netherlands Cancer Institute, Amsterdam, the Netherlands
  • 2Department of Urology, Radboud University Hospital, Nijmegen, the Netherlands
  • 3Department of Urology, Princess Margaret Hospital, Toronto, Ontario, Canada
  • 4Department of Oncology, Cardiff Hospital, Wales, United Kingdom
  • 5Department of Urology, Institut Jules Bordet, Brussels, Belgium
  • 6Department of Urology, Amsterdam Medical Center, Amsterdam University, Amsterdam, the Netherlands
  • 7Division of Medical Oncology, QEII Health Sciences Center, Halifax, Nova Scotia, Canada
  • 8Department of Urology, Saint Antonius Hospital, Nieuwegein, the Netherlands
  • 9Department of Oncology, Maastricht University Medical Center, Maastricht, the Netherlands
  • 10Department of Surgery-Urology, University of Montreal Hospital Center, Quebec, Ontario, Canada
  • 11Department of Oncology, The Royal Free Hospital and Queen Mary University, London, United Kingdom
  • 12Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  • 13Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
  • 14Department of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  • 15Department of Statistics, European Organisation for Research and Treatment of Cancer, Brussels, Belgium
  • 16Currently with Bristol-Myers Squibb, Brussels, Belgium
JAMA Oncol. Published online December 13, 2018. doi:10.1001/jamaoncol.2018.5543
Key Points

Question  Does a period of sunitinib therapy before cytoreductive nephrectomy improve outcomes in patients with renal cancer compared with immediate cytoreductive nephrectomy followed by sunitinib therapy?

Findings  In this randomized clinical trial of 99 patients, the progression-free rate at 28 weeks did not improve when patients began sunitinib therapy before planned cytoreductive nephrectomy; however, more patients received systemic therapy, and cytoreductive nephrectomy could be avoided in those with progressive disease.

Meaning  Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned cytoreductive nephrectomy without inferior outcome.

Abstract

Importance  In clinical practice, patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown.

Objective  To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib.

Design, Setting, and Participants  This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied.

Interventions  Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy.

Main Outcomes and Measures  Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points.

Results  The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P = .61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95; P = .03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%).

Conclusions and Relevance  Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib.

Trial Registration  ClinicalTrials.gov identifier: NCT01099423.

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