Randomized, Double-Blind Phase III Study of Pazopanib Versus Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease After Metastasectomy: ECOG-ACRIN E2810.

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 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.

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.

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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024 Mar 26 [Epub ahead of print]

Leonard J Appleman, Se Eun Kim, Wayne B Harris, Sumanta K Pal, Michael R Pins, Jill Kolesar, Neeraj Agarwal, Rahul A Parikh, Daniel A Vaena, Christopher W Ryan, Mehmood Hashmi, Brian A Costello, David Cella, Janice P Dutcher, Robert S DiPaola, Naomi B Haas, Lynne I Wagner, Michael A Carducci

UPMC Hillman Cancer Center, Pittsburgh, PA., Dana-Farber Cancer Institute, Boston, MA., Emory University and Atlanta VA Medical Center, Atlanta, GA., City of Hope Comprehensive Cancer Center, Duarte, CA., Rosalind Franklin University, Chicago, IL., University of Kentucky, Lexington, KY., Huntsman Cancer Institute, University of Utah, Salt Lake City, UT., University of Kansas, Kansas City, KS., West Cancer Center, Germantown, TN., University of Oregon Health & Science University, Portland, OR., Stormont-Vail HealthCare, Topeka, KS., Mayo Clinic, Rochester, MN., Northwestern University Feinberg School of Medicine, Chicago, IL., Our Lady of Mercy, Bronx, NY., Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA., Wake Forest University, Winston-Salem, NC., Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.