PET-CR as a potential surrogate endpoint in untreated DLBCL: meta-analysis and implications for clinical trial design
Language English Country United States Media print-electronic
Document type Meta-Analysis, Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Bayesian hierarchical model, clinical trial simulation, diffuse large B-cell lymphoma, end-of-treatment PET-complete response, meta-analysis, progression-free and overall survival,
- MeSH
- Bayes Theorem MeSH
- Biomarkers analysis MeSH
- Lymphoma, Large B-Cell, Diffuse * diagnostic imaging drug therapy MeSH
- Clinical Trials as Topic MeSH
- Humans MeSH
- Disease-Free Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers MeSH
This study's focus is the association of end-of-therapy (EOT) PET results with progression-free (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma receiving first-line chemoimmunotherapy. We develop a Bayesian hierarchical model for predicting PFS and OS from EOT PET-complete response (PET-CR) using a literature-based meta-analysis of 20 treatment arms and a substudy of 4 treatment arms in 3 clinical trials for which we have patient-level data. The PET-CR rate in our substudy was 72%. The modeled estimates for hazard ratio (PET-CR/non-PET-CR) were 0.13 for PFS (95% CI 0.10, 0.16) and 0.10 for OS (CI 0.07, 0.12). Hazard ratios varied little by patient subtype and were confirmed by the overall meta-analysis. We link these findings to designing future clinical trials and show how our model can be used in adapting the sample size of a trial to accumulating results regarding treatment benefits on PET-CR and a survival endpoint.
BC Cancer Agency Vancouver BC Canada
Berry Consultants LLC Austin TX USA
Candiolo Cancer Institute FPO IRCCS Candiolo Italy
Charles University and General University Hospital Prague Czech Republic
Department of Nuclear Medicine University of Virginia Charlottesville VA USA
Department of Translational and Precision Medicine Sapienza Università di Roma Rome Italy
F Hoffmann La Roche Ltd Basel Switzerland
University Libraries Texas A and M University College Station TX USA
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