Statistical aspects in adjuvant and neoadjuvant trials for gastrointestinal cancer in 2020: focus on time-to-event endpoints.

PURPOSE OF REVIEW: Clinical-trial design, analysis, and interpretation entails the use of efficient and reliable endpoints. Statistical issues related to endpoints warrant continued attention, as they may have a substantial impact on the conduct of clinical trials and on interpretation of their results. RECENT FINDINGS: We review concepts and discuss recent developments related to the use of time-to-event endpoints in studies on adjuvant and neoadjuvant therapy for colon, pancreatic, and gastric adenocarcinomas. The definition of endpoints has varied to a considerable extent in these settings. Although these variations are relevant in interpreting results from individual trials, they probably have a small impact when considered in aggregate. In terms of surrogacy, most published reports so far have used aggregated data. A few studies based on the preferred method of a metaanalysis of individual-patient data have shown that disease-free survival (DFS) is a surrogate for overall survival in the adjuvant therapy of stage III colon cancer and in gastric cancer, whereas DFS with a landmark of six months is a surrogate for overall survival in the neoadjuvant therapy of adenocarcinoma of the esophagus, gastroesophageal junction, or stomach. SUMMARY: Testing novel agents in gastrointestinal cancer requires continued attention to statistical issues related to endpoints.