Pharmacokinetic/pharmacodynamic relationship of therapeutic monoclonal antibodies used in oncology: Part 2, immune checkpoint inhibitor antibodies
| Autor: | Louis Blondel, Christophe Maritaz, Julia Delahousse, Angelo Paci, Aude Desnoyer, Olivier Mir, Sophie Broutin, Nathalie Chaput |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Metabolic Clearance Rate medicine.drug_class Programmed Cell Death 1 Receptor Pembrolizumab Pharmacology Monoclonal antibody B7-H1 Antigen 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Immune system Antigen Atezolizumab Neoplasms Tumor Microenvironment Humans Medicine CTLA-4 Antigen Tissue Distribution Dose-Response Relationship Drug biology business.industry Immunogenicity Antibodies Monoclonal Treatment Outcome 030104 developmental biology Clinical Trials Phase III as Topic Oncology 030220 oncology & carcinogenesis biology.protein Drug Monitoring Nivolumab Antibody business Half-Life |
| Zdroj: | European Journal of Cancer. 128:119-128 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2020.01.003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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