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
Year: 2024
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: 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.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco.23.01544
Authors: 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
Institutions: UPMC Hillman Cancer Center, Dana-Farber Cancer Institute, Emory University, Atlanta VA Medical Center, City Of Hope National Medical Center, Rosalind Franklin University of Medicine and Science, University of Kentucky, Huntsman Cancer Institute, University of Kansas, West Cancer Center, Oregon Health & Science University, Stormont Vail Health, Mayo Clinic, Northwestern University, Lady of Mercy Medical Center, Abramson Cancer Center, University of Pennsylvania, Wake Forest University, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1881030900, ECOG-ACRIN Network Group Operations Center, G1938688226, G2167093779, G2727264567, G2819266960, G3100437649, G3231584006, G3475623468, G399916856, G4017138494, G4340946455, ECOG-ACRIN NCORP Research Base, G5417201949, G545695214, G580335595, G6536185887, G6705915398, G6710502012, G6952446453, Johns Hopkins University NCTN Lead Academic Site Program, G8220656038, Alliance for Clinical Trials in Oncology Operations Center, G9000097678, G9000224436, G9000280145, G9000319834, G9000327439
OpenAlex ID: W4393259381