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
[1]
A. Belldegrun,et al.
Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma: The ARISER Randomized Clinical Trial
,
2017,
JAMA oncology.
[2]
J. Patard,et al.
Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.
,
2016,
The New England journal of medicine.
[3]
Stuart J Pocock,et al.
The Primary Outcome Fails - What Next?
,
2016,
The New England journal of medicine.
[4]
J. Manola,et al.
Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial
,
2016,
The Lancet.
[5]
S. Pal,et al.
Adjuvant therapy for renal cell carcinoma: past, present, and future.
,
2014,
The oncologist.
[6]
R. Thompson,et al.
Assessment of the pathologic inclusion criteria from contemporary adjuvant clinical trials for predicting disease progression after nephrectomy for renal cell carcinoma
,
2012,
Cancer.
[7]
J. Lam,et al.
Postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma based on a validated prognostic nomogram and risk group stratification system.
,
2005,
The Journal of urology.
[8]
J. Cooper.
Ajcc Cancer Staging Manual
,
1997
.
[9]
D. Cox.
Regression Models and Life-Tables
,
1972
.
[10]
D.,et al.
Regression Models and Life-Tables
,
2022
.