Abstract
IMPORTANCE: Given recently published results of a 750-patient adjuvant sunitinib trial showing improved disease-free survival (DFS), the appropriate strategy for treating high-risk patients is unclear. We sought to determine whether there is improved disease-free survival benefit to taking the active drug in patients with high-risk (pT3, pT4, node-positive) clear cell renal cancer (ccRCC) in the ASSURE trial (adjuvant sunitinib or sorafenib vs placebo in resected unfavorable renal cell carcinoma [RCC]), the largest adjuvant trial published to date. OBJECTIVE: To evaluate DFS and overall survival (OS) in ccRCC high-risk patients randomized to sunitinib or sorafenib vs placebo among patients with stages comparable to other high-risk adjuvant trials. DESIGN, SETTING, AND PARTICIPANTS: The DFS and OS at 10 years postactivation were calculated for 1069 patients in US and Canadian cooperative groups with high-risk patients who had ccRCC histology and pT3, pT4, or node-positive disease accrued between 2006 and 2010 to the double-blind randomized placebo-controlled phase 3 trial. Outcome analyses by dose quartiles of these patients receiving sunitinib or sorafenib were also performed. INTERVENTIONS: Patients received 1 year of adjuvant sunitinib (50 mg), sorafenib (800 mg) daily, or equivalent placebo. The study was amended for patient intolerance to sunitinib (37.5 mg), sorafenib (400 mg) daily, or equivalent placebo with mandatory dose escalation if no serious adverse effects were experienced. MAIN OUTCOMES AND MEASURES: Disease-free survival, defined as time from randomization to recurrence, second primary cancer, or death. RESULTS: Of 1069 patients, 358 (243 [67.9%] men, 115 [32.1%] women) received sunitinib, 355 (248 [69.9%] men, 107 [30.1%] women) received sorafenib, and 356 (254 [71.3%] men, 102 [28.7%] women) received placebo as adjuvant therapy. The mean (SD) age for each group was 58.3 (10.6) years, 56.8 (10.3) years, and 57.5 (10.4) years, respectively. Five-year DFS rates were 47.7%, 49.9%, and 50.0%, respectively for sunitinib, sorafenib, and placebo (HR, 0.94 for sunitinib vs placebo; and HR, 0.90; 97.5% CI, 0.71-1.14 for sorafenib vs placebo), with 5-year OS of 75.2%, 80.2%, and 76.5% (HR, 1.06; 97.5% CI, 0.78-1.45; P = .66, sunitinib vs placebo; and HR, 0.80; 97.5% CI, 0.58-1.11; P = .12 for sorafenib vs placebo). There was no difference by dose quartile. CONCLUSIONS AND RELEVANCE: Neither prognostic category of the tumor nor dose intensity of therapy altered the lack of difference in DFS or OS in this population of patients with high-risk ccRCC. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00326898.
Original language | English |
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Pages (from-to) | 1249-1252 |
Number of pages | 4 |
Journal | JAMA Oncology |
Volume | 3 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2017 |
Bibliographical note
Funding Information:Funding/Support: This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA180820, CA180794, CA180867, CA180821, CA31946, CA077202, CA180863, CCSRI021039, CA32102, CA105409, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. The trial was supported by the Cancer Trials Evaluation Program, National Cancer Institute, who provided drugs and placebos through agreements with Bayer and Pfizer.
Publisher Copyright:
© 2017 American Medical Association. All rights reserved.
ASJC Scopus subject areas
- Oncology
- Cancer Research