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Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy
A mixed effect model describing median overall survival (mOS) in patients with advanced hepatocellular carcinoma (aHCC) treated with antiangiogenic therapy (AAT) was developed from literature data. Data were extracted from 59 studies, representing 4,813 patients. The final model included estimates o...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879476/ https://www.ncbi.nlm.nih.gov/pubmed/27299940 http://dx.doi.org/10.1002/psp4.12078 |
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author | Zierhut, ML Chen, Y Pithavala, YK Nickens, DJ Valota, O Amantea, MA |
author_facet | Zierhut, ML Chen, Y Pithavala, YK Nickens, DJ Valota, O Amantea, MA |
author_sort | Zierhut, ML |
collection | PubMed |
description | A mixed effect model describing median overall survival (mOS) in patients with advanced hepatocellular carcinoma (aHCC) treated with antiangiogenic therapy (AAT) was developed from literature data. Data were extracted from 59 studies, representing 4,813 patients. The final model included estimates of mOS after AAT (8.5 months) or placebo (7.1 months) administration. The mOS increased 21% when the AAT was sorafenib (SOR) or 42% when locoregional therapy was coadministered. The mOS decreased when patients received prior systemic therapy (↓7%) or concomitant chemotherapy (↓4%) or the percentage of patients with hepatitis B increased (↓∼0.4%/%). Clinical trial simulations of a phase II comparative trial predicted an mOS ratio (placebo:AAT) of 0.687 or 0.831, with a 65% or 22% probability of demonstrating superiority, for SOR or other AATs, respectively. Additionally, the 95% confidence interval (CI) of the simulated median mOS ratio for non‐SOR AATs was similar to the 95% CI of the hazard ratio (HR) observed in the trial. |
format | Online Article Text |
id | pubmed-4879476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48794762016-06-21 Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy Zierhut, ML Chen, Y Pithavala, YK Nickens, DJ Valota, O Amantea, MA CPT Pharmacometrics Syst Pharmacol Original Articles A mixed effect model describing median overall survival (mOS) in patients with advanced hepatocellular carcinoma (aHCC) treated with antiangiogenic therapy (AAT) was developed from literature data. Data were extracted from 59 studies, representing 4,813 patients. The final model included estimates of mOS after AAT (8.5 months) or placebo (7.1 months) administration. The mOS increased 21% when the AAT was sorafenib (SOR) or 42% when locoregional therapy was coadministered. The mOS decreased when patients received prior systemic therapy (↓7%) or concomitant chemotherapy (↓4%) or the percentage of patients with hepatitis B increased (↓∼0.4%/%). Clinical trial simulations of a phase II comparative trial predicted an mOS ratio (placebo:AAT) of 0.687 or 0.831, with a 65% or 22% probability of demonstrating superiority, for SOR or other AATs, respectively. Additionally, the 95% confidence interval (CI) of the simulated median mOS ratio for non‐SOR AATs was similar to the 95% CI of the hazard ratio (HR) observed in the trial. John Wiley and Sons Inc. 2016-05-15 2016-05 /pmc/articles/PMC4879476/ /pubmed/27299940 http://dx.doi.org/10.1002/psp4.12078 Text en © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Zierhut, ML Chen, Y Pithavala, YK Nickens, DJ Valota, O Amantea, MA Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy |
title | Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy |
title_full | Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy |
title_fullStr | Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy |
title_full_unstemmed | Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy |
title_short | Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy |
title_sort | clinical trial simulations from a model‐based meta‐analysis of studies in patients with advanced hepatocellular carcinoma receiving antiangiogenic therapy |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879476/ https://www.ncbi.nlm.nih.gov/pubmed/27299940 http://dx.doi.org/10.1002/psp4.12078 |
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