Pharmacokinetic/pharmacodynamic relationship of therapeutic monoclonal antibodies used in oncology: Part 2, immune checkpoint inhibitor antibodies

被引:63
作者
Desnoyer, Aude [1 ,2 ]
Broutin, Sophie [3 ]
Delahousse, Julia [3 ]
Maritaz, Christophe [1 ]
Blondel, Louis [1 ]
Mir, Olivier [4 ]
Chaput, Nathalie [1 ,2 ]
Paci, Angelo [1 ,3 ]
机构
[1] Univ Paris Saclay, Fac Pharm, F-92290 Chatenay Malabry, France
[2] Lab Immunomonitoring Oncol, Gustave Roussy Canc Campus, F-94805 Villejuif, France
[3] Dept Pharmacol, Gustave Roussy Canc Campus, F-94805 Villejuif, France
[4] Dept Ambulatory Care, Gustave Roussy Canc Campus, F-94805 Villejuif, France
关键词
Checkpoint inhibitors; Pharmacokinetics; Pharmacodynamic properties; Therapeutic drug monitoring; Cancer; CLINICAL ACTIVITY; PHASE-I; NIVOLUMAB EXPOSURE; DOSE-ESCALATION; SOLID TUMOR; IPILIMUMAB; PHARMACOKINETICS; PEMBROLIZUMAB; SAFETY; CANCER;
D O I
10.1016/j.ejca.2020.01.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2020 Elsevier Ltd. All rights reserved.
引用
收藏
页码:119 / 128
页数:10
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