Guidelines for the definition of time to event endpoints in renal cell cancer clinical trials: results of the DATECAN project.
Fiche publication
Date publication
septembre 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Pr JACQMIN Didier
Tous les auteurs :
Kramar A, Negrier S, Sylvester R, Joniau S, Mulders P, Powles T, Bex A, Bonnetain F, Bossi A, Bracarda S, Bukowski R, Catto J, Choueiri TK, Crabb S, Eisen T, El Demery M, Fitzpatrick J, Flamand V, Goebell PJ, Gravis G, Houede N, Jacqmin D, Kaplan R, Malavaud B, Massard C, Melichar B, Mourey L, Nathan P, Pasquier D, Porta C, Pouessel D, Quinn D, Ravaud A, Rolland F, Schmidinger M, Tombal B, Tosi D, Vauleon E, Volpe A, Wolter P, Escudier B, Filleron T
Lien Pubmed
Résumé
BACKGROUND: In clinical trials, the use of intermediate time to event endpoints (TEE) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for endpoint definitions. MATERIAL AND METHODS: A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the non-metastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each endpoint. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent endpoints and the associated events. RESULTS: Thirty-four experts scored 121 events for 9 endpoints. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds respectively. In the NM setting: Disease-Free Survival (contralateral renal cell cancer, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), Metastasis-Free Survival (appearance of metastases, regional recurrence, death from RCC); and Local Regional Free-Survival (local or regional recurrence, death from RCC). In the MA setting: Kidney Cancer Specific Survival (death from RCC or protocol treatment) and Progression-Free Survival (death from RCC, Local, regional, or metastatic progression). CONCLUSIONS: The consensus method revealed that intermediate endpoints have not been well defined, since all of the selected endpoints had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons.
Référence
Ann Oncol. 2015 Sep 14. pii: mdv380.