A Kramar1, S Negrier2, R Sylvester3, S Joniau4, P Mulders5, T Powles6, A Bex7, F Bonnetain8, A Bossi9, S Bracarda10, R Bukowski11, J Catto12, T K Choueiri13, S Crabb14, T Eisen15, M El Demery16, J Fitzpatrick17, V Flamand18, P J Goebell19, G Gravis20, N Houédé21, D Jacqmin22, R Kaplan23, B Malavaud24, C Massard9, B Melichar25, L Mourey26, P Nathan27, D Pasquier28, C Porta29, D Pouessel30, D Quinn31, A Ravaud32, F Rolland33, M Schmidinger34, B Tombal35, D Tosi36, E Vauleon37, A Volpe38, P Wolter39, B Escudier9, T Filleron40. 1. Methodology and Biostatistics Unit, Centre Oscar Lambret and SIRIC ONCO LILLE, Lille. 2. Department of Medical Oncology, University of Lyon I, Centre Léon Bérard, Lyon, France. 3. Department of Biostatistics, EORTC Headquarters, Brussels. 4. Department of Urology, University Hospitals Leuven, Leuven, Belgium. 5. Department of Urology, Radboud University Medical Centre, Nijmegan, The Netherlands. 6. Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK. 7. Department of Urology, The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis, Amsterdam, The Netherlands. 8. Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon. 9. Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France. 10. Department of Oncology, Ospedale San Donato, Arezzo, Italy. 11. Department of Immunology, Cleveland Clinic Taussig Cancer Center, Cleveland, USA. 12. Academic Urology Unit, University of Sheffield, Sheffield, UK. 13. Kidney Cancer Center, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, USA. 14. Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton. 15. Department of Oncology, Cambridge University Health Partners, Cambridge, UK. 16. Department of Medical Oncology, University Hospital of Nîmes, Nimes, France. 17. Division of Surgery, Mater Misericordiae Hospital and University College Dublin, Dublin, Ireland. 18. Department of Urology, University Lille2 Nord de France, Lille, France. 19. Department of Urology, Friedrich-Alexander University Erlangen-Nueremberg, Erlangen, Germany. 20. Department of Medical Oncology, Institut Paoli-Calmettes, Marseille. 21. Department of Medical Oncology, CHU Caremeau, Nîmes. 22. Department of Urology, CHRU, Strasbourg, France. 23. MRC Clinical Trials Unit, University College London, London, UK. 24. Department of Urology, CHU, Toulouse, France. 25. Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic. 26. Department of Medical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer-Oncopole, Toulouse, France. 27. Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, Middlesex, UK. 28. Department of Academic Radiation Oncology, Centre Oscar Lambret and SIRIC ONCO LILLE, Lille, France. 29. Department of Medical Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 30. Department of Medical Oncology, Hôpital Saint-Louis, APHP, Paris, France. 31. Division of Oncology, USC Norris Comprehensive Cancer Center and Hospital, Los Angeles, USA. 32. Department of Medical Oncology, Hôpital Saint André, Bordeaux. 33. Department of Medical Oncology, Institut de cancérologie de l'Ouest-René Gauducheau, Nantes, France. 34. Department of Medicine I, Clinical Division of Oncology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 35. Department of Urology, Cliniques Universitaires Saint Luc, Brussels, Belgium. 36. Department of Medical Oncology, Institut Régional du Cancer Val d'Aurelle, Montpellier. 37. Department of Medical Oncology, Centre Eugène Marquis, Rennes, France. 38. Division of Urology, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy. 39. Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. 40. Department of Medical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer-Oncopole, Toulouse, France filleron.thomas@iuct-oncopole.fr.
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 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 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.
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 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 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.
Authors: Romain Cohen; Dewi Vernerey; Carine Bellera; Aurélia Meurisse; Julie Henriques; Xavier Paoletti; Benoît Rousseau; Steven Alberts; Thomas Aparicio; Ioannis Boukovinas; Sharlene Gill; Richard M Goldberg; Axel Grothey; Tetsuya Hamaguchi; Timothy Iveson; Rachel Kerr; Roberto Labianca; Sara Lonardi; Jeffrey Meyerhardt; James Paul; Cornelis J A Punt; Leonard Saltz; Marck P Saunders; Hans-Joachim Schmoll; Manish Shah; Alberto Sobrero; Ioannis Souglakos; Julien Taieb; Atsuo Takashima; Anna Dorothea Wagner; Marc Ychou; Franck Bonnetain; Sophie Gourgou; Takayuki Yoshino; Greg Yothers; Aimery de Gramont; Qian Shi; Thierry André Journal: Eur J Cancer Date: 2020-03-12 Impact factor: 9.162
Authors: Wanling Xie; Susan Halabi; Jayne F Tierney; Matthew R Sydes; Laurence Collette; James J Dignam; Marc Buyse; Christopher J Sweeney; Meredith M Regan Journal: JNCI Cancer Spectr Date: 2019-02-06
Authors: Tobias Klatte; Kevin M Gallagher; Luca Afferi; Alessandro Volpe; Nils Kroeger; Silvia Ribback; Alan McNeill; Antony C P Riddick; James N Armitage; Tevita F 'Aho; Tim Eisen; Kate Fife; Axel Bex; Allan J Pantuck; Grant D Stewart Journal: BMC Med Date: 2019-10-03 Impact factor: 8.775