title: Adjuvant Treatment for High-Risk Clear Cell Renal Cancer: Updated Results of a High-Risk Subset of the ASSURE Randomized Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00326898.
authors.affiliation: Abramson Cancer Center of the University of Pennsylvania, Philadelphia.
authors.forename: Naomi B
authors.initials: NB
authors.lastname: Haas
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Judith
authors.initials: J
authors.lastname: Manola
authors.affiliation: Cancer Research Foundation, New York, New York.
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Washington, DC.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.affiliation: Formerly at Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.|Currently at University of Kentucky College of Medicine, Louisville.
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib