title: Association between treatment effects on disease progression end points and overall survival in clinical studies of patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  The relationship between progression-free survival and time to progression (PFS/TTP) and overall survival (OS) has been demonstrated in a variety of solid tumours but not in metastatic renal cell carcinoma (mRCC).
  
  
  METHODS
  A systematic literature search was conducted to identify controlled trials of cytokine or targeted therapies for mRCC reporting information on treatment effects on PFS/TTP and OS for one or more comparison. The associations between treatment effects on PFS/TTP and OS were analysed using linear regression.
  
  
  RESULTS
  Thirty-one studies representing 10943 patients, 75 treatment groups, and 41 comparisons were identified. The correlation coefficient between the negative log of the hazard ratio (HR) for PFS/TTP (-ln HR(PFS/TTP)) vs the negative log of the HR for OS (-ln HR(OS)) was 0.80 (P<0.0001). In linear regression, the coefficient on -ln HR(PFS/TTP) vs -ln HR(OS) was 0.64 (95% confidence interval (CI): 0.470.81; R(2)=0.63), suggesting each 10% relative risk reduction (RRR) for PFS/TTP was associated with a 6% RRR for OS. A 1-month gain in median PFS/TTP was associated with a 1.17-month gain in median OS (95% CI: 0.59,1.76; R(2)=0.28).
  
  
  CONCLUSIONS
  In trials of treatments for mRCC, treatment effects on PFS/TTP are strongly associated with treatment effects on OS.
authors.affiliation: PAI (Policy Analysis Inc.), 4 Davis Court, Brookline, MA 02445, USA. tdelea@pai2.com
authors.forename: T E
authors.initials: TE
authors.lastname: Delea
authors.forename: A
authors.initials: A
authors.lastname: Khuu
authors.forename: D Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: T
authors.initials: T
authors.lastname: Haas
authors.forename: D
authors.initials: D
authors.lastname: Soulières
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome