Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors.

Clinical Pharmacokinetics
Maddalena CentanniJ G Coen van Hasselt

Abstract

Immune checkpoint inhibitors (ICIs) have demonstrated significant 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 clarification 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 significant healthcare costs associated with these agents, arguments for both dose individualization and generalization are provided. We address important issues related to the efficacy 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 benefiting from treatment with ICIs have been brought forward. However, validated ...Continue Reading

References

Mar 18, 2005·Annual Review of Immunology·Rebecca J GreenwaldArlene H Sharpe
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomonori TawaraShiro Kataoka
Sep 12, 2008·Clinical Pharmacology and Therapeutics·W WangJ P Balthasar
Nov 26, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jedd D WolchokF Stephen Hodi
Dec 2, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tanja Schneider-MerckMichael Dechant
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Jul 9, 2010·Clinical Pharmacokinetics·Ron J KeizerJos H Beijnen
Sep 10, 2010·Journal of the National Cancer Institute·Axel HoosJedd Wolchok
Jun 7, 2011·The New England Journal of Medicine·Caroline RobertJedd D Wolchok
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
May 23, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jeffrey S WeberAxel Hauschild
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Jun 5, 2012·The New England Journal of Medicine·Julie R BrahmerJon M Wigginton
Aug 29, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A Hoos
Dec 12, 2012·British Journal of Clinical Pharmacology·Johan G C van HasseltAlwin D R Huitema
Apr 23, 2013·British Journal of Clinical Pharmacology·J G Coen van HasseltAlwin D R Huitema
Apr 30, 2013·Journal of Leukocyte Biology·Andrew M Intlekofer, Craig B Thompson
May 15, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Liza C Villaruz, Mark A Socinski
Jun 7, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yan FengJeffrey S Weber
Jul 31, 2013·Immunity·Daniel S Chen, Ira Mellman
Jan 18, 2014·British Journal of Clinical Pharmacology·Yan FengAmit Roy
Mar 5, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Suzanne L TopalianF Stephen Hodi
Apr 4, 2015·Science·Padmanee Sharma, James P Allison
Apr 22, 2015·The New England Journal of Medicine·Caroline RobertUNKNOWN KEYNOTE-006 investigators
May 16, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Amita PatnaikAnthony W Tolcher
Jun 2, 2015·The New England Journal of Medicine·James LarkinJedd D Wolchok
Aug 13, 2015·Clinical Pharmacology and Therapeutics·T H Oude MunninkP Brummelhuis-Visser
Aug 28, 2015·CPT: Pharmacometrics & Systems Pharmacology·Jgc van HasseltAdr Huitema
Sep 15, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Zeynep ErogluAntoni Ribas
Oct 16, 2015·Drug Discovery Today. Technologies·J G Coen van Hasselt, Piet H van der Graaf
Nov 13, 2015·American Journal of Clinical Oncology·Elizabeth I Buchbinder, Anupam Desai
Nov 13, 2015·European Journal of Haematology·Barbara Jezeršek Novaković
Jan 15, 2016·Blood·Stephen A BeersAnn L White
Feb 24, 2016·Oncogenesis·P E Porporato
Apr 16, 2016·Nature Reviews. Cancer·Suzanne L TopalianDrew M Pardoll
Apr 28, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M ChatterjeeØ Fløtten
May 5, 2016·Nature Reviews. Clinical Oncology·Celine BoutrosCaroline Robert

❮ Previous
Next ❯

Citations

Feb 14, 2020·International Journal of Dermatology·Nolan J MaloneyScott Worswick
Dec 13, 2019·Journal of Cancer Research and Clinical Oncology·Rui KitadaiYukio Hosomi
Nov 9, 2019·Clinical Pharmacokinetics·Etienne ChatelutGérard Milano
Jan 20, 2020·Clinical Pharmacology and Therapeutics·Yulia VugmeysterAkash Khandelwal
Oct 28, 2019·Clinical Pharmacokinetics·Belén P SolansIñaki F Trocóniz
Apr 24, 2020·British Journal of Clinical Pharmacology·Yara AbdouMarc S Ernstoff
May 20, 2020·British Journal of Clinical Pharmacology·Cody J PeerMark J Ratain
May 13, 2020·British Journal of Clinical Pharmacology·Geoffrey Alan WatsonAnna Spreafico
Jun 10, 2020·Cancers·Clément BaillyMichel Chérel
Aug 29, 2020·Future Oncology·Maryam SoleimaniChristian Kollmannsberger
Sep 3, 2020·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Ivette Mourani PadrónFernando Gutiérrez Nicolás
Oct 3, 2020·Expert Opinion on Biological Therapy·Samer A Al Hadidi, Hun Ju Lee
Jan 9, 2020·Journal of Nephrology·Natalie C SteinelMichael W Lee
Aug 9, 2020·Frontiers in Oncology·Andreas SaltosAlberto Chiappori
May 10, 2020·British Journal of Clinical Pharmacology·Vishal NavaniAndre Van Der Westhuizen
Apr 1, 2020·Frontiers in Pharmacology·Maddalena Centanni, Lena E Friberg
May 15, 2020·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·Tienush RassafUNKNOWN Committee for Clinical Cardiovascular Medicine of the German Cardiac Society
Nov 24, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Diego EnricoBenjamin Besse
Sep 2, 2020·Annual Review of Pharmacology and Toxicology·Arthur GeraudJoe-Elie Salem
Jan 24, 2021·Cancer Immunology, Immunotherapy : CII·Iris KamerJair Bar
Feb 16, 2021·World Journal of Virology·Asim KichlooAkif Kichloo
Nov 25, 2020·Cancers·Maria-Carlota Londoño On Behalf Of The Retoinmuno Multidisciplinary Group
Feb 15, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M SuredaJ Rebollo
Dec 11, 2020·The Cancer Journal·Mitchell S von ItzsteinDavid E Gerber
Mar 2, 2021·Journal of Clinical Apheresis·Frances ComptonNicole De Simone
Mar 12, 2021·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Fabian JunkerHenry Kao
Mar 22, 2021·Pharmacology Research & Perspectives·Etienne ChatelutDirk Jan A R Moes
Apr 28, 2021·Cancer Chemotherapy and Pharmacology·Mathilde MarchandRené Bruno

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme-linked immunosorbent assays
biopsies

Clinical Trials Mentioned

NCT00135408
NCT00289627
NCT00289640
NCT00261365
NCT02108652
NCT02031458
NCT01375842
NCT02155647
NCT01772004
NCT01943461

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2022 Meta ULC. All rights reserved