Author(s): Leonard J. Appleman, MD, PhD1, Se Eun Kim, MB2, Wayne B. Harris, MD3, Sumanta K. Pal, MD4, Michael R. Pins, MD5, Jill Kolesar, PharmD, MS6, Neeraj Agarwal, MD7, Rahul A. Parikh, MD, PhD8, Daniel A. Vaena, MD9, Christopher W. Ryan, MD10, Mehmood Hashmi, MD11, Brian A. Costello, MD12, David Cella, PhD13, Janice P. Dutcher, MD14, Naomi B. Haas, MD15, Lynne I. Wagner, PhD16, Michael A. Carducci, MD17, Robert S. DiPaola, MD6
PURPOSE
Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy.
PATIENTS AND METHODS
Patients with NED after metastasectomy were randomly assigned 1:1 to receive pazopanib 800 mg once daily versus placebo for 52 weeks. The study was designed to observe an improvement in DFS from 25% to 45% with pazopanib at 3 years, corresponding to 42% reduction in the DFS event rate.
RESULTS
From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events (92% information). The study did not meet its primary end point. An updated analysis at 60.5-month median follow-up from random assignment (95% CI, 59.3 to 71.0) showed that the 3-year DFS was 27.4% (95% CI, 17.9 to 41.7) for pazopanib and 21.9% (95% CI, 13.3 to 36.2) for placebo. Hazard ratio (HR) for DFS was 0.90 ([95% CI, 0.60 to 1.34]; Pone-sided = .29) in favor of pazopanib. Three-year overall survival (OS) was 81.9% (95% CI, 72.7 to 92.2) for pazopanib and 91.4% (95% CI, 84.4 to 98.9) for placebo. The HR for OS was 2.55 (95% CI, 1.23 to 5.27) in favor of placebo (Ptwo-sided = .012). Health-related quality-of-life measures deteriorated in the pazopanib group during the treatment period.
CONCLUSION
Pazopanib did not improve DFS as the primary end point compared with blinded placebo in patients with mRCC with NED after metastasectomy. In addition, there was a concerning trend favoring placebo in OS.
Author Affiliations
1UPMC Hillman Cancer Center, Pittsburgh, PA, 2Dana-Farber Cancer Institute, Boston, MA, 3Emory University and Atlanta VA Medical Center, Atlanta, GA, 4City of Hope Comprehensive Cancer Center, Duarte, CA, 5Rosalind Franklin University, Chicago, IL, 6University of Kentucky, Lexington, KY, 7Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 8University of Kansas, Kansas City, KS, 9West Cancer Center, Germantown, TN, 10University of Oregon Health & Science University, Portland, OR, 11Stormont-Vail HealthCare, Topeka, KS, 12Mayo Clinic, Rochester, MN, 13Northwestern University Feinberg School of Medicine, Chicago, IL, 14Our Lady of Mercy, Bronx, NY, 15Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, 16Wake Forest University, Winston-Salem, NC, 17Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
