A case for time to tumor progression (TTP) as the primary (1o) efficacy endpoint in 1st-line metastatic colorectal cancer (MCRC) therapy: Correlation of TTP and overall survival (OS)

3503 Background: OS has been the 1o endpoint for phase III MCRC registration trials. However, increasing numbers of efficacious agents have extended OS and added therapeutic complexity. Evaluation of new drugs based on OS may be impeded by larger sample sizes, longer study durations, and crossovers. Thus, FDA, ASCO and AACR, in a review of surrogate and clinical benefit endpoints, have asked if TTP could replace OS as the 1o endpoint because it measures an early treatment effect and is not confounded by later therapies. Methods: As part of this effort, we assessed the relationship of TTP to OS in the 1o patient data from the 2 large, FDA-reviewed phase III trials (NEJM, 343:905, 2001; Lancet 355:1041, 2001) that form the basis of irinotecan/5-FU/leucovorin (IFL) approval in previously untreated MCRC. Patients (pts) were randomized to: Study 1 (bolus IFL or FL or I) and Study 2 (infusional IFL or FL) and could receive 2nd-line I or FL; 2nd-line oxaliplatin was not widely available. Results: The linear regr...