Prediction of survival benefits from progression-free survival in patients with advanced non small cell lung cancer: Evidence from a pooled analysis of 2,838 patients randomized in 7 trials

Abstract

8019 Background: Survival benefits can be predicted from progression-free survival in advanced colorectal cancer (Buyse et al, JCO 2007; 25:5218), but not in advanced breast cancer (Burzykowski et al, JCO 2007; in press). We investigated whether progression-free survival (PFS) could be considered a valid surrogate for overall survival (OS) in patients with advanced non small cell lung cancer (NSCLC). Methods: Individual patient data were collected from all trials comparing docetaxel to vinca alkaloids for the first-line treatment of patients with NSCLC (Douillard et al, J Thoracic Oncol 2007;2:939). Surrogacy of PFS for OS was assessed through the association between these endpoints and between the treatment effects on these endpoints. Treatment effects were estimated through hazard ratios in the 322 participating centers. Centers with less than 3 patients per treatment arm were grouped. Squared correlation coefficients were estimated along with their 95% confidence interval (CI). The surrogate threshold effect was defined as the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS in a future trial. Results: The median follow-up of patients still alive was 23.4 months, median OS 10.0 months, median PFS 5.5 months. PFS was correlated with OS (R² = 0.68, CI = 0.676 - 0.681), with PFS explaining two thirds of the variance in OS. The treatment effects on PFS and on OS were also correlated (R² = 0.83, CI = 0.62 - 1.05), with treatment effects on PFS explaining four fifths of the variance in treatment effects on OS. The surrogate threshold effect was a PFS hazard ratio of 0.70, indicating that a risk reduction of 30% in terms of PFS predicts a significant effect on OS. Conclusions: PFS may be an acceptable surrogate for OS in future trials in advanced NSCLC. Treatments that reduce the PFS hazard by at least 30% are expected to lead to significant benefits in terms of overall survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Alfacell Corporation Alfacell, Amgen, AstraZeneca, Boehringer Ingelheim, Hoffmann-La Roche, Lilly Alfacell, Alfacell Corporation Bayer Healthcare, Boehringer Ingelheim, Hoffmann-La Roche, Lilly, Pierre Fabre Merck