Surrogate endpoints for overall survival (OS) in head and neck squamous cell carcinoma (HNSCC): Evaluation using individual data of 23,737 patients

6035 Background: The gold standard endpoint in randomized trials of HNSCC is OS. Our objective was to study if event-free survival (EFS) or loco-regional control (LRC) could be good surrogate endpoints to estimate the effect of radiotherapy (RT) and chemotherapy (CT) on OS. This would permit to decrease the duration and cost of the development of new treatments for HNSCC. Methods: EFS is the time from randomization to first event (loco-regional, distant recurrence or death), LRC the time from randomization to first loco-regional event. Individual patient data from two meta-analyses (MARCH; Bourhis, Lancet 2006, MACH-NC; Bourhis, ASCO 2004) were used. At the individual level, the rank correlation coefficient ρ between the surrogate endpoint (EFS or LRC) and OS was estimated from the bivariate distribution of these endpoints. At the trial level, the correlation coefficient R between treatment effects (estimated by log hazard ratios) on the surrogate endpoint and OS was estimated from a linear regression. EFS and LRC would be acceptable surrogates only if the correlation coefficients ρ and R were close to 1. Results: At the individual level, EFS was more strongly correlated with OS than LRC. For RT, treatment effects on both LRC and EFS were strongly correlated with those on OS. For CT, the correlation coefficients between treatment effects on EFS and OS were larger than those between LRC and OS. Conclusions: The preliminary analysis indicates that EFS can be used as a surrogate for OS to evaluate the treatment effect in randomized trials of patients with HNSCC. LRC is a possible alternative in RT alone trials. Unrestricted grants from ARC, LNCC, PHRC, Sanofi-Aventis. [Table: see text] [Table: see text]