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dc.contributor.authorShi, Qen_US
dc.contributor.authorSchmitz, Nen_US
dc.contributor.authorOu, F-Sen_US
dc.contributor.authorDixon, JGen_US
dc.contributor.authorCunningham, Den_US
dc.contributor.authorPfreundschuh, Men_US
dc.contributor.authorSeymour, JFen_US
dc.contributor.authorJaeger, Uen_US
dc.contributor.authorHabermann, TMen_US
dc.contributor.authorHaioun, Cen_US
dc.contributor.authorTilly, Hen_US
dc.contributor.authorGhesquieres, Hen_US
dc.contributor.authorMerli, Fen_US
dc.contributor.authorZiepert, Men_US
dc.contributor.authorHerbrecht, Ren_US
dc.contributor.authorFlament, Jen_US
dc.contributor.authorFu, Ten_US
dc.contributor.authorCoiffier, Ben_US
dc.contributor.authorFlowers, CRen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2018-11-20T12:07:32Z
dc.date.issued2018-09-01en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29975624en_US
dc.identifier.citationJ Clin Oncol, 2018, 36 (25), pp. 2593 - 2602en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2949
dc.identifier.eissn1527-7755en_US
dc.identifier.doi10.1200/JCO.2018.77.9124en_US
dc.description.abstractPurpose Overall survival (OS) is the definitive and best-established primary efficacy end point to evaluate diffuse large B-cell lymphoma (DLBCL) therapies, but it requires prolonged follow-up. An earlier end point assessed post-treatment would expedite clinical trial conduct and accelerate patient access to effective new therapies. Our objective was to formally evaluate progression-free survival (PFS) and PFS at 24 months (PFS24) as surrogate end points for OS in first-line DLBCL. Patients and Methods Individual patient data were analyzed from 7,507 patients from 13 multicenter randomized controlled trials of active treatment in previously untreated DLBCL, published after 2002, with sufficient PFS data to predict treatment effects on OS. Trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS was evaluated using both linear regression ( R2WLS) and Copula bivariable ( R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80 and neither < 0.7, with lower-bound 95% CI > 0.60. Results Trial-level surrogacy for PFS was strong ( R2WLS = 0.83; R2Copula = 0.85) and met the predefined criteria for surrogacy. At the patient level, PFS strongly correlated with OS. The surrogate threshold effect had a hazard ratio of 0.89. Surrogacy was consistent across comparisons with or without rituximab and with rituximab maintenance trials. Trial-level surrogacy for PFS24 was relatively strong ( R2WLS = 0.77; R2Copula = 0.78) but did not meet prespecified criteria. At the patient level, PFS24 significantly correlated with OS. The surrogate threshold effect had an odds ratio of 1.51. Conclusion This large pooled analysis of individual patient data supports PFS as a surrogate end point for OS in future randomized controlled trials evaluating chemoimmunotherapy in DLBCL. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before OS results are mature.en_US
dc.format.extent2593 - 2602en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.titleProgression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Diffuse Large B-Cell Lymphoma: An Individual Patient-Level Analysis of Multiple Randomized Trials (SEAL).en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1200/JCO.2018.77.9124en_US
rioxxterms.licenseref.startdate2018-09-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJ Clin Oncolen_US
pubs.issue25en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume36en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
dc.contributor.icrauthorCunningham, Daviden_US


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