Investigation of disease-free survival as a surrogate endpoint for survival in cancer clinical trials

A stochastic model wiuh exponential components is used to describe our data collected from a phase III cancer clinical trial. Criteria which guarantee that disease-free survival (DFS) can be used as a surrogate for overall survival are explored under this model. We examine several colorectal adjuvant clinical trials and find that these conditions are not satisfied. The relationship between the hazard ratio of DFS for an active treatment versus a control treatment and the cumulative hazard ratio of survival for the same two treatments is then explored. An almost linear relationship is found such that a hazard ratio for DFS of less than a threshold R corresponds to a non-null treatment effect on survival The threshold value R is determined for our colorectal adjuvant trial data. Based on this relationship, a one-sided test of equal hazard rate of survival is equivalent to a test of hazard ratio of DFS small than R This approach assumes that recurrence information is unbiasedly and accurately assessed; an assumpion which is sometimes difficult to ensure for multicenter clinical trials, particularly for interim analyses.