Progression-free survival (PFS) as a surrogate for overall survival (OS) in patients with advanced colorectal cancer: An analysis of 3159 patients randomized in 11 trials

3513 Background: The traditional endpoint for efficacy in advanced colorectal cancer is OS, but this endpoint requires prolonged follow-up and the impact of first-line therapy on OS may be confounded by the effect of second-line therapies. We investigate whether PFS can replace OS as the primary endpoint in randomized trials on patients with advanced colorectal cancer. Methods: Individual patient data were available from 11 randomized phase III trials comparing 5-fluorouracil (5FU) + folinic acid (LV) to either 5FU alone (8 trials, 1814 patients) or raltitrexed (3 trials, 1345 patients). The correlation between PFS and OS was estimated through the bivariate distribution of these endpoints over the entire time range, or using Kaplan-Meier estimates of 6-month PFS and 12-month OS within each trial. The correlation between the treatment effects on PFS and OS was estimated using the hazard ratios over the entire time range, or up until 6 months for PFS and 12 months for OS. Correlation coefficients were estim...