Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: Results of the DATECAN project

A. Kramar, S. Negrier, R. Sylvester, S. Joniau, P. Mulders, T. Powles, A. Bex, F. Bonnetain, A. Bossi, S. Bracarda, R. Bukowski, J. Catto, T. K. Choueiri, S. Crabb, T. Eisen, M. El Demery, J. Fitzpatrick, V. Flamand, P. J. Goebell, G. GravisN. Houédé, D. Jacqmin, R. Kaplan, B. Malavaud, C. Massard, B. Melichar, L. Mourey, P. Nathan, D. Pasquier, C. Porta, D. Pouessel, D. Quinn, A. Ravaud, F. Rolland, M. Schmidinger, B. Tombal, D. Tosi, E. Vauleon, A. Volpe, P. Wolter, B. Escudier, T. Filleron, Sylvie Negrier, Steven Joniau, Peter Mulders, Thomas Powles, Bernard Escudier, Axel Bex, Franck Bonnetain, Alberto Bossi, Sergio Braccarda, Ronald Bukowski, James Catto, Toni Choueiri, Simon Crabb, Tim Eisen, Mounira El Demery, John Fitzpatrick, Vincent Flamand, Peter J. Goebell, Gwendael Gravis, Nadine Houédé, Didier Jacqmin, Richard Kaplan, Bernard Malavaud, Christophe Massard, Bohuslav Melichar, Loïc Mourey, Paul Nathan, David Pasquier, Camillo Porta, Damien Pouessel, David Quinn, Alain Ravaud, Frédéric Rolland, Manuela Schmidinger, Bertrand Tombal, Diego Tosi, Elodie Vauleon, Alessandro Volpe, P. Pascal Wolter

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In clinical trials, the use of intermediate time-to-event end points (TEEs) 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 end point definitions. Materials and methods: A formalmodified 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 nonmetastatic (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 end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. Results: Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, 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 end points have not been well defined, because all of the selected end points 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.

Original languageEnglish
Pages (from-to)2392-2398
Number of pages7
JournalAnnals of Oncology
Volume26
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

Keywords

  • Clinical trials
  • DATECAN
  • Recommendations
  • Renal cell cancer
  • Time-to-event end points

ASJC Scopus subject areas

  • Oncology
  • Hematology

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