Progression-free survival and time to progression as surrogate markers of overall survival in patients with advanced gastric cancer: Literature-based analysis of 36 randomized trials.

Abstract

103 Background: We evaluated the potential of progression-free survival (PFS) and time to progression (TTP) to act as surrogates of overall survival (OS) in clinical trial settings by a comprehensive literature-based analysis. Methods: Randomized trials of systemic chemotherapy for advanced gastric cancer were identified by comprehensive electronic and manual search. Correlations between PFS/TTP and OS were evaluated. Results: Thirty-six trials with a total of 83 treatment arms and 10,484 patients were selected for analysis. The nonparametric Spearman rank correlation coefficient (p) between median PFS/TTP and OS was 0.70 (95% CI, 0.59 to 0.82) and the correlation coefficient between hazard ratios in PFS/TTP and OS was 0.80 (95% CI, 0.68 to 0.92). Correlation tended to be higher in non-Asian (p = 0.80; 0.61-0.98) than Asian trials (p = 0.67; 0.39-0.94), higher in trials reporting PFS (p = 0.85; 0.72-0.97) than in those reporting TTP (p = 0.60; 0.24-0.97), and higher in trials in patients with measurable lesions only (p = 0.91; 0.77-1.00) than in those including non-measurable lesions (p = 0.71; 0.50-0.93), albeit that none of these differences was significant. Conclusions: Our results indicate that improvements in PFS/TTP in advanced gastric cancer strongly correlate with improvements in OS. PFS/TTP may be an appropriate surrogate for OS in clinical trials for advanced gastric cancer. No significant financial relationships to disclose.