title: Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial.
abstract: OBJECTIVE
  Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in patients with renal cell carcinoma (RCC) are reported.
  
  
  METHODS
  Nine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated.
  
  
  RESULTS
  The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio [HR] = 0.88; P = .146); however, when post-cross-over placebo survival data were censored, the difference became significant (17.8 v 14.3 months, respectively; HR = 0.78; P = .029). Adverse events at 16 months after cross over were similar to those previously reported. Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status (P < .0001), Memorial Sloan-Kettering Cancer Center score (P < .0001), and PFS and OS in univariate (PFS, P = .0013; OS, P = .0009) and multivariate (PFS, P = .0231; OS, P = .0416) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib (P = .0145). Both high-VEGF (P < .01) and low-VEGF (P < .01) groups benefited from sorafenib.
  
  
  CONCLUSIONS
  Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC.
authors.affiliation: Institut Gustave Roussy, Villejuif, France. escudier@igr.fr
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Cezary
authors.initials: C
authors.lastname: Szczylik
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.forename: Michael
authors.initials: M
authors.lastname: Staehler
authors.forename: Sylvie
authors.initials: S
authors.lastname: Negrier
authors.forename: Christine
authors.initials: C
authors.lastname: Chevreau
authors.forename: Apurva A
authors.initials: AA
authors.lastname: Desai
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rolland
authors.forename: Tomasz
authors.initials: T
authors.lastname: Demkow
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: Martin
authors.initials: M
authors.lastname: Gore
authors.forename: Sibyl
authors.initials: S
authors.lastname: Anderson
authors.forename: Gloria
authors.initials: G
authors.lastname: Hofilena
authors.forename: Minghua
authors.initials: M
authors.lastname: Shan
authors.forename: Carol
authors.initials: C
authors.lastname: Pena
authors.forename: Chetan
authors.initials: C
authors.lastname: Lathia
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy*; D018592:Cross-Over Studies; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009325:Nausea / Q000139:chemically induced; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000077157:Sorafenib