Pharmacokinetic/pharmacodynamic relationship of therapeutic monoclonal antibodies used in oncology: Part 2, immune checkpoint inhibitor antibodies.
Antibodies, Monoclonal
/ pharmacology
Antineoplastic Agents, Immunological
/ pharmacology
B7-H1 Antigen
/ antagonists & inhibitors
CTLA-4 Antigen
/ antagonists & inhibitors
Clinical Trials, Phase III as Topic
Dose-Response Relationship, Drug
Drug Monitoring
Half-Life
Humans
Metabolic Clearance Rate
Neoplasms
/ blood
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Tissue Distribution
Treatment Outcome
Tumor Microenvironment
/ drug effects
Cancer
Checkpoint inhibitors
Pharmacodynamic properties
Pharmacokinetics
Therapeutic drug monitoring
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
10
11
2019
revised:
02
01
2020
accepted:
07
01
2020
pubmed:
11
2
2020
medline:
9
10
2020
entrez:
11
2
2020
Statut:
ppublish
Résumé
Immune checkpoint inhibitors are monoclonal antibodies (mAbs) directed against negative immunologic regulators that are used to restore the immune response against cancer. Approved drugs include anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death-ligand 1 (PD-L1) antibodies exhibiting pharmacokinetic (PK) characteristics typical of mAbs. Most factors such as age, sex, ethnicity, tumour burden, performance status and immunogenicity, but not body weight, do not seem to affect drug clearance clinically. However, an exposure-response relation has been described for both the efficacy and toxicity of anti-CTLA-4 and anti-PD-1 agents. The change in clearance over time is associated with overall response at least for nivolumab and pembrolizumab. Few PK/pharmacodynamic (PD) data are available for anti-PD-L1 mAbs, but time-varying clearance has been described for these drugs, and the high immunogenicity rate observed with atezolizumab may affect PK parameters and should be further studied. These data suggest the need for additional PK/PD studies. In this review, we summarise studies of the PKs of immune checkpoint inhibitors, exploring possible interactions with PD considerations.
Identifiants
pubmed: 32037060
pii: S0959-8049(20)30005-8
doi: 10.1016/j.ejca.2020.01.003
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
CD274 protein, human
0
CTLA-4 Antigen
0
CTLA4 protein, human
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
119-128Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement O.M. receives consultancy fees from Amgen, Astra-Zeneca, Bayer, Blueprint Medicines, Bristol Myers-Squibb, Eli-Lilly, Incyte, Ipsen Biopharmaceuticals, Lundbeck, MSD, Novartis, Pfizer, Roche, Servier and Vifor Pharma, is member of advisory boards of Amgen, Astra-Zeneca, Bayer, Blueprint Medicines, Bristol Myers-Squibb, Eli-Lilly, Lundbeck, MSD, Novartis, Pfizer, Roche, Servier and Vifor Pharma, participates in a speaker's bureaus of Eli-Lilly, Roche and Servier and holds stock in Amplitude surgical and Transgene. A.P. receives consultancy fees from Amgen and is member of advisory boards of Pierre Fabre, Fresenius and Pfizer. C.M. is employed in Oncology medical department at Boehringer-Ingelheim, with no competing interest in this project. Other authors have nothing to disclose.