Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) have demonstrated signifcant clinical impact in improving overall survival of several malignancies associated with poor outcomes; however, only 20–40% of patients will show long-lasting survival. Further clarifcation of factors related to treatment response can su...

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Autores: Centanni, M. (Maddalena)|||/items/09a9d68e-0002-4991-bb99-0d7684645467, Moes, D.J.A.R. (Dirk Jan A. R.)|||/items/f540cc8d-8372-4216-8ab1-8b9afdad1ecd, Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44, Ciccolini, J. (Joseph)|||/items/fd12a9f6-96e3-4574-a8c3-60da4aa15d2f, Coen-van-Hasselt, J.G. (J. G.)|||/items/0d68d8ef-19a4-464b-81f7-5f58db2096dc
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/62591
Acceso en línea:https://hdl.handle.net/10171/62591
Access Level:acceso abierto
Palabra clave:Pharmacokinetics (PK)
iImmune checkpoint inhibitors (ICIs)
Pharmacodynamics (PD)
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spelling Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint InhibitorsCentanni, M. (Maddalena)|||/items/09a9d68e-0002-4991-bb99-0d7684645467Moes, D.J.A.R. (Dirk Jan A. R.)|||/items/f540cc8d-8372-4216-8ab1-8b9afdad1ecdTroconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44Ciccolini, J. (Joseph)|||/items/fd12a9f6-96e3-4574-a8c3-60da4aa15d2fCoen-van-Hasselt, J.G. (J. G.)|||/items/0d68d8ef-19a4-464b-81f7-5f58db2096dcPharmacokinetics (PK)iImmune checkpoint inhibitors (ICIs)Pharmacodynamics (PD)Immune checkpoint inhibitors (ICIs) have demonstrated signifcant clinical impact in improving overall survival of several malignancies associated with poor outcomes; however, only 20–40% of patients will show long-lasting survival. Further clarifcation of factors related to treatment response can support improvements in clinical outcome and guide the development of novel immune checkpoint therapies. In this article, we have provided an overview of the pharmacokinetic (PK) aspects related to current ICIs, which include target-mediated drug disposition and time-varying drug clearance. In response to the variation in treatment exposure of ICIs and the signifcant healthcare costs associated with these agents, arguments for both dose individualization and generalization are provided. We address important issues related to the efcacy and safety, the pharmacodynamics (PD), of ICIs, including exposure–response relationships related to clinical outcome. The unique PK and PD aspects of ICIs give rise to issues of confounding and suboptimal surrogate endpoints that complicate interpretation of exposure–response analysis. Biomarkers to identify patients benefting from treatment with ICIs have been brought forward. However, validated biomarkers to monitor treatment response are currently lacking.Springer Science and Business Media LLCDadun. Depósito Académico Digital Universidad de Navarra20212021-11-1720192019-01-0120192019-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/62591reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/625912026-06-21T12:47:57Z
dc.title.none.fl_str_mv Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
title Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
spellingShingle Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
Centanni, M. (Maddalena)|||/items/09a9d68e-0002-4991-bb99-0d7684645467
Pharmacokinetics (PK)
iImmune checkpoint inhibitors (ICIs)
Pharmacodynamics (PD)
title_short Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
title_full Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
title_fullStr Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
title_full_unstemmed Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
title_sort Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
dc.creator.none.fl_str_mv Centanni, M. (Maddalena)|||/items/09a9d68e-0002-4991-bb99-0d7684645467
Moes, D.J.A.R. (Dirk Jan A. R.)|||/items/f540cc8d-8372-4216-8ab1-8b9afdad1ecd
Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44
Ciccolini, J. (Joseph)|||/items/fd12a9f6-96e3-4574-a8c3-60da4aa15d2f
Coen-van-Hasselt, J.G. (J. G.)|||/items/0d68d8ef-19a4-464b-81f7-5f58db2096dc
author Centanni, M. (Maddalena)|||/items/09a9d68e-0002-4991-bb99-0d7684645467
author_facet Centanni, M. (Maddalena)|||/items/09a9d68e-0002-4991-bb99-0d7684645467
Moes, D.J.A.R. (Dirk Jan A. R.)|||/items/f540cc8d-8372-4216-8ab1-8b9afdad1ecd
Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44
Ciccolini, J. (Joseph)|||/items/fd12a9f6-96e3-4574-a8c3-60da4aa15d2f
Coen-van-Hasselt, J.G. (J. G.)|||/items/0d68d8ef-19a4-464b-81f7-5f58db2096dc
author_role author
author2 Moes, D.J.A.R. (Dirk Jan A. R.)|||/items/f540cc8d-8372-4216-8ab1-8b9afdad1ecd
Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44
Ciccolini, J. (Joseph)|||/items/fd12a9f6-96e3-4574-a8c3-60da4aa15d2f
Coen-van-Hasselt, J.G. (J. G.)|||/items/0d68d8ef-19a4-464b-81f7-5f58db2096dc
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Pharmacokinetics (PK)
iImmune checkpoint inhibitors (ICIs)
Pharmacodynamics (PD)
topic Pharmacokinetics (PK)
iImmune checkpoint inhibitors (ICIs)
Pharmacodynamics (PD)
description Immune checkpoint inhibitors (ICIs) have demonstrated signifcant clinical impact in improving overall survival of several malignancies associated with poor outcomes; however, only 20–40% of patients will show long-lasting survival. Further clarifcation of factors related to treatment response can support improvements in clinical outcome and guide the development of novel immune checkpoint therapies. In this article, we have provided an overview of the pharmacokinetic (PK) aspects related to current ICIs, which include target-mediated drug disposition and time-varying drug clearance. In response to the variation in treatment exposure of ICIs and the signifcant healthcare costs associated with these agents, arguments for both dose individualization and generalization are provided. We address important issues related to the efcacy and safety, the pharmacodynamics (PD), of ICIs, including exposure–response relationships related to clinical outcome. The unique PK and PD aspects of ICIs give rise to issues of confounding and suboptimal surrogate endpoints that complicate interpretation of exposure–response analysis. Biomarkers to identify patients benefting from treatment with ICIs have been brought forward. However, validated biomarkers to monitor treatment response are currently lacking.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01
2019
2019-01-01
2021
2021-11-17
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/62591
url https://hdl.handle.net/10171/62591
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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