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dc.contributor.authorBurzykowski, Tomasz-
dc.contributor.authorCoart, Elisabeth-
dc.contributor.authorSaad, Everardo D-
dc.contributor.authorShi, Qian-
dc.contributor.authorSommeijer, Dirkje W-
dc.contributor.authorBokemeyer, Carsten-
dc.contributor.authorDíaz-Rubio, Eduardo-
dc.contributor.authorDouillard, Jean-Yves-
dc.contributor.authorFalcone, Alfredo-
dc.contributor.authorFuchs, Charles S-
dc.contributor.authorGoldberg, Richard M-
dc.contributor.authorHecht, J Randolph-
dc.contributor.authorHoff, Paulo M-
dc.contributor.authorHurwitz, Herbert-
dc.contributor.authorKabbinavar, Fairooz F-
dc.contributor.authorKoopman, Miriam-
dc.contributor.authorMaughan, Timothy S-
dc.contributor.authorPunt, Cornelis J A-
dc.contributor.authorSaltz, Leonard-
dc.contributor.authorSchmoll, Hans-Joachim-
dc.contributor.authorSeymour, Matthew T-
dc.contributor.authorTebbutt, Niall C-
dc.contributor.authorTournigand, Christophe-
dc.contributor.authorVan Cutsem, Eric-
dc.contributor.authorde Gramont, Aimery-
dc.contributor.authorZalcberg, John R-
dc.contributor.authorBuyse, Marc-
dc.identifier.citationJAMA network open 2019; 2(9): e1911750-
dc.description.abstractTumor measurements can be used to estimate time to nadir and depth of nadir as potential surrogates for overall survival (OS). To assess time to nadir and depth of nadir as surrogates for OS in metastatic colorectal cancer. Pooled analysis of 20 randomized clinical trials within the Aide et Recherche en Cancerologie Digestive database, which contains academic and industry-sponsored trials, was conducted. Three sets of comparisons were performed: chemotherapy alone, antiangiogenic agents, and anti-epidermal growth factor receptor agents in first-line treatment for patients with metastatic colorectal cancer. Surrogacy of time to nadir and depth of nadir was assessed at the trial level based on joint modeling of relative tumor-size change vs baseline and OS. Treatment effects on time to nadir and on depth of nadir were defined in terms of between-arm differences in time to nadir and in depth of nadir, and both were assessed in linear regressions for their correlation with treatment effects (hazard ratios) on OS within each set. The strengths of association were quantified using sample-size-weighted coefficients of determination (R2), with values closer to 1.00 indicating stronger association. At the patient level, the correlation was assessed between modeled relative tumor-size change and OS. For 14 chemotherapy comparisons in 4289 patients, the R2 value was 0.63 (95% CI, 0.30-0.96) for the association between treatment effects on time to nadir and OS and 0.08 (95% CI, 0-0.37) for depth of nadir and OS. For 11 antiangiogenic agent comparisons (4854 patients), corresponding values of R2 were 0.25 (95% CI, 0-0.72) and 0.06 (95% CI, 0-0.35). For 8 anti-epidermal growth factor receptor comparisons (2684 patients), corresponding values of R2 were 0.24 (95% CI, 0-0.83) and 0.21 (95% CI, 0-0.78). In contrast with early reports favoring depth of response as a surrogate, these results suggest that neither time to nadir nor depth of nadir is an acceptable surrogate for OS in the first-line treatment of metastatic colorectal cancer.-
dc.titleEvaluation of Continuous Tumor-Size-Based End Points as Surrogates for Overall Survival in Randomized Clinical Trials in Metastatic Colorectal Cancer.-
dc.typeJournal Article|Meta-Analysis|Research Support, Non-U.S. Gov't-
dc.identifier.journaltitleJAMA network open-
dc.identifier.affiliationUniversity Hospital S Chiara, Pisa, Italyen
dc.identifier.affiliationInternational Drug Development Institute, Louvain-la-Neuve, Belgiumen
dc.identifier.affiliationAcademic Medical Centre, Amsterdam, the Netherlandsen
dc.identifier.affiliationFlevohospital, Almere, the Netherlandsen
dc.identifier.affiliationKatholieke Universiteit, Leuven, Belgiumen
dc.identifier.affiliationHasselt University, Diepenbeek, Belgiumen
dc.identifier.affiliationInternational Drug Development Institute Inc, San Francisco, Californiaen
dc.identifier.affiliationCentre René Gauducheau, St Herblain, Franceen
dc.identifier.affiliationHôpital Henri Mondor, Creteil, Franceen
dc.identifier.affiliationFranco-British Institute, Levallois-Perret, Franceen
dc.identifier.affiliationDivision of Digestive Oncology, University Hospitals Gasthuisberg Leuven, Leuven, Belgiumen
dc.identifier.affiliationThe University of Sydney, Camperdown, New South Wales, Australiaen
dc.identifier.affiliationAustin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationSchool of Public Health and Preventative Medicine, Monash University, Melbourne, Australiaen
dc.identifier.affiliationDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota-
dc.identifier.affiliationDepartment of Internal Medicine II and Clinic, University of Hamburg, Hamburg, Germany-
dc.identifier.affiliationHospital Clinico San Carlos and Centro de Investigación Biomédica en Red Cáncer, CIBERONC, Madrid, Spain-
dc.identifier.affiliationDana-Farber Cancer Institute, Boston, Massachusetts-
dc.identifier.affiliationWest Virginia University Cancer Institute, Morgantown-
dc.identifier.affiliationDavid Geffen School of Medicine, University of California, Los Angeles-
dc.identifier.affiliationInstituto de Câncer do Estado de São Paulo, São Paulo, Brazil-
dc.identifier.affiliationGenentech, South San Francisco, California-
dc.identifier.affiliationDavid Geffen School of Medicine, University of California, Los Angeles-
dc.identifier.affiliationDepartment of Medical Oncology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands-
dc.identifier.affiliationCancer Research UK and the Medical Research Council Oxford Institute for Radiation Oncology, Oxford, United Kingdom-
dc.identifier.affiliationAmsterdam University Medical Centrum, Department of Medical Oncology, University of Amsterdam, Amsterdam, the Netherlands-
dc.identifier.affiliationMemorial Sloan-Kettering Cancer Center, New York, New York-
dc.identifier.affiliationMartin-Luther University, Halle, Germany-
dc.identifier.affiliationSt James's Hospital, University of Leeds, Leeds, United Kingdom-
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