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Randomized, double-blind phase III study of pazopanib versus placebo in patients with metastatic renal cell carcinoma who have no evidence of disease following metastasectomy: A trial of the ECOG-ACRIN cancer research group (E2810)

  • Leonard Joseph Appleman,
  • Maneka Puligandla,
  • Sumanta K. Pal,
  • Wayne Harris,
  • Neeraj Agarwal,
  • Brian Addis Costello,
  • Christopher W. Ryan,
  • Michael Pins,
  • Jill Kolesar,
  • Daniel A. Vaena,
  • Rahul Atul Parikh,
  • Mehmood Hashmi,
  • Janice P. Dutcher,
  • Robert S. DiPaola,
  • Naomi B. Haas,
  • Michael Anthony Carducci
UPMC Hillman Cancer Center, Pittsburgh, PA Dana-Farber Cancer Institute, Boston, MA City of Hope National Medical Center, Duarte, CA Emory University School of Medicine, Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA University of Utah Huntsman Cancer Institute, Salt Lake City, UT Mayo Clinic, Rochester, MN Oregon Health & Science University, Knight Cancer Institute, Portland, OR University of Illinois College of Medicine, Chicago, IL University of Wisconsin Carbone Cancer Center, Madison, WI University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City, IA University of Kansas Cancer Center, Westwood, KS University of Kansas, Kansas City, KS Cancer Research Foundation of NY, Bronx, NY University of Kentucky, Lexington, KY Penn Medicine Abramson Cancer Center, Philadelphia, PA Sidney Kimmel Cancer Center At Johns Hopkins, Baltimore, MD

Patients with no evidence of disease (NED) after metastasectomy for metastatic renal cell carcinoma (mRCC) are at high risk of recurrence, but no systemic therapy has been shown to benefit this population. Pazopanib is an inhibitor of VEGFR and other kinases that improves progression-free survival in patients with measurable RCC metastatic disease. We performed a randomized, double-blind, placebo-controlled multicenter study to test the hypothesis that pazopanib would improve disease-free survival in patients with mRCC rendered NED after metastasectomy.

Patients with NED following metastasectomy were randomized 1:1 to receive pazopanib starting at 800 mg daily vs. placebo for 52 weeks. Patients were stratified by 1 vs.> 1 site of resected disease, and by disease-free interval ≤vs.> 1 year. Clinical assessment for toxicity and patient-reported outcomes were performed every 4 weeks, and restaging scans every 12 weeks. The study was designed to observe a 42% improvement in disease-free survival (DFS) from 25% to 45% at 3 years.

From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events had been observed (92% information). The median follow-up from randomization was 30 months (range 0.4 – 66.5 months). The study did not meet the primary endpoint: hazard ratio (95% CI) for DFS was 0.85 (0.55, 1.31) p= 0.47 in favor of pazopanib. At the time of unblinding, 22/129 (17%) of subjects had died. The HR for overall survival (OS) was 2.65 (1.02, 6.9) in favor of placebo (p= 0.05). Patient-reported outcomes and laboratory correlates will be reported separately.

52 weeks of pazopanib did not improve DFS compared to blinded placebo in patients with mRCC who were NED after metastasectomy. There was a trend toward worse overall survival with pazopanib. Clinical trial information: NCT01575548.