title: Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-alpha) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported.
  
  
  METHODS
  Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-alpha 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up.
  
  
  RESULTS
  Median overall survival was greater in the sunitinib group than in the IFN-alpha group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-alpha group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor-signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-alpha (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-alpha (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%).
  
  
  CONCLUSIONS
  Sunitinib demonstrates longer overall survival compared with IFN-alpha plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. motzerr@mskcc.org
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: Piotr
authors.initials: P
authors.lastname: Tomczak
authors.forename: M Dror
authors.initials: MD
authors.lastname: Michaelson
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.forename: Sylvie
authors.initials: S
authors.lastname: Negrier
authors.forename: Cezary
authors.initials: C
authors.lastname: Szczylik
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: Xavier
authors.initials: X
authors.lastname: Garcia-del-Muro
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Ewa
authors.initials: E
authors.lastname: Solska
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.forename: Sindy T
authors.initials: ST
authors.lastname: Kim
authors.forename: Isan
authors.initials: I
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011336:Probability; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D016898:Interferon-alpha; D011758:Pyrroles; D000077210:Sunitinib