Disease-Free Survival as a Surrogate for Overall Survival in Adjuvant Trials of Gastric Cancer: A Meta-Analysis

Abstract

In investigations of the effectiveness of surgery and adjuvant chemotherapy for gastric cancers, overall survival (OS) is considered the gold standard endpoint. However, the disadvantage of using OS as the endpoint is that it requires an extended follow-up period. We sought to investigate whether disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant chemotherapy for gastric cancer. The GASTRIC group initiated a meta-analysis of individual patient data collected in randomized clinical trials comparing adjuvant chemotherapy vs surgery alone for patients with curatively resected gastric cancer. Surrogacy of DFS was assessed through the correlation between the endpoints as well as through the correlation between the treatment effects on the endpoints. External validation of the prediction based on DFS was also evaluated. Individual patient data from 14 randomized clinical trials that included a total of 3288 patients were analyzed. The rank correlation coefficient between DFS and OS was 0.974 (95% confidence interval [CI] 0.971 to 0.976). The coefficient of determination between the treatment effects on DFS and on OS was as high as 0.964 (95% CI 0.926 to 1.000), and the surrogate threshold effect based on adjusted regression analysis was 0.92. In external validation, the six hazard ratios for OS predicted according to DFS were in very good agreement with those actually observed for OS. DFS is an acceptable surrogate for OS in trials of cytotoxic agents for gastric cancer in the adjuvant setting.