Disease-free survival is not a surrogate endpoint for overall survival in adjuvant trials of pancreatic cancer: a systematic review of randomized trials.

BACKGROUND: Adjuvant chemotherapy (CT) is the standard of care for patients with resected pancreatic cancer (PC). Overall survival (OS) has traditionally represented the primary endpoint in randomized trials assessing adjuvant therapies for PC. The aim of this study was to assess if disease-free survival (DFS) was an adequate surrogate endpoint for OS in randomized trials of adjuvant therapy in PC.

METHODS: A systematic literature search was conducted in PubMed, Web of Science, SCOPUS and Embase, Cochrane Library and the World Health Organization International Clinical Trials Registry Platform up to February 2nd, 2017. Surrogacy of DFS with OS was assessed between endpoints and OS through the Spearman rank correlation coefficient, and between the treatment effects on the endpoints using the squared correlation R2 .

RESULTS: A total of 12 eligible randomized trials that enrolled 4,888 patients where identified for the final analysis. Correlation of DFS with OS was weak at the individual level (Spearman rank correlation coefficient = 0.31) and moderate at the trial level (R2  = 0.44).

CONCLUSIONS: DFS does not represent an appropriate surrogate for OS in randomized trials of adjuvant therapy for resected PC. Hence, OS should remain the primary endpoint of future trials evaluating new agents in postsurgical setting.