Association between treatment effects on disease progression end points and overall survival in clinical studies of patients with metastatic renal cell carcinoma

Br J Cancer. 2012 Sep 25;107(7):1059-68. doi: 10.1038/bjc.2012.367. Epub 2012 Aug 30.

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).

Conclusion: In trials of treatments for mRCC, treatment effects on PFS/TTP are strongly associated with treatment effects on OS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / drug therapy*
  • Disease Progression
  • Disease-Free Survival
  • Endpoint Determination
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Molecular Targeted Therapy
  • Randomized Controlled Trials as Topic
  • Survival Analysis
  • Treatment Outcome