Guidelines for time-to-event end-point definitions in adjuvant randomised trials for patients with localised colon cancer: Results of the DATECAN initiative.

BACKGROUND

The variability of definitions for time-to-event (TTE) end-points impacts the conclusions of randomised clinical trials (RCTs). The Definition for the Assessment of Time-to-event Endpoints in CANcer (DATECAN) initiative aims to provide consensus definitions for TTE end-points used in RCTs. Here, we formulate guidelines for adjuvant colon cancer RCTs.

METHODS

We performed a literature review to identify TTE end-points and events included in their definition in RCT publications. Then, a consensus was reached among a panel of international experts, using a formal modified Delphi method, with 2 rounds of questionnaires and an in-person meeting.

RESULTS

Twenty-four experts scored 72 events involved in 6 TTE end-points. Consensus was reached for 24%, 57% and 100% events after the first round, second round and in-person meeting. For RCTs not using overall survival as their primary end-point, the experts recommend using disease-free survival (DFS) rather than recurrence-free survival (RFS) or time to recurrence (TTR) as the primary end-point. The consensus definition of DFS includes all causes of death, second primary colorectal cancers (CRCs), anastomotic relapse and metastatic relapse as an event, but not second primary non-CRCs. Events included in the RFS definition are the same as for DFS with the exception of second primary CRCs. The consensus definition of TTR includes anastomotic or metastatic relapse, death with evidence of recurrence and death from CC cause.

CONCLUSION

Standardised definitions of TTE end-points ensure the reproducibility of the end-points between RCTs and facilitate cross-trial comparisons. These definitions should be integrated in standard practice for the design, reporting and interpretation of adjuvant CC RCTs.

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement L.S. has received research funds from Taiho Pharmaceutical. M.S. has received honoraria for meetings/lectures from Roche, Merck, Sanofi, Servier and Amgen. R.C. has received honoraria from Amgen, Sanofi and Servier and travel fees from Sanofi. T.A. has served in a consulting/advisory role, and/or received honoraria from Amgen, Bristol-Myers Squibb, Chugai, HalioDx, MSD Oncology, Pierre Fabre, Roche/Ventana, Sanofi and Servier and has received travel accommodations and expenses from Roche/Genentech, MSD Oncology and Bristol-Myers Squibb. T.Y. has received funding from Novartis Pharma K.K., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Chugai Pharmaceutical Co. Ltd., Sanofi K.K., Daiichi Sankyo Co. Ltd., PAREXEL International Inc. and Ono Pharmaceutical Co. Ltd. ADW reports personal fees from Bristol-Myers Squibb, Servier Suisse, Merck , Merck Sharp & Dohme, Bayer, EMD Serono, Lilly, Sanofi, and Celgene, non-financial support from AstraZeneca, AbbVie, Sanofi-Adventis Deutchland, SHIRE, and PFIZER. All remaining authors have declared no conflicts of interest.