M&S Decisions LLC, Moscow, Russia.
PK Sciences Modeling & Simulation, Novartis Institutes of BioMedical Research, Cambridge, MA, USA.
Oncoimmunology. 2020 May 21;9(1):1748982. doi: 10.1080/2162402X.2020.1748982.
Programmed cell death-1 (PD-1) and/or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint inhibitor (ICI) treatments are associated with adverse events (AEs), which may be dependent on ICI dose. Applying a model-based meta-analysis to evaluate safety data from published clinical trials from 2005 to 2018, we analyzed the dose/exposure dependence of ICI treatment-related AE (trAE) and immune-mediated AE (imAE) rates. Unlike with PD-1 inhibitor monotherapy, CTLA-4 inhibitor monotherapy exhibited a dose/exposure dependence on most AE types evaluated. Furthermore, combination therapy with PD-1 inhibitor significantly strengthened the dependence of trAE and imAE rates on CTLA-4 inhibitor dose/exposure.
程序性细胞死亡受体-1（PD-1）和/或细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）免疫检查点抑制剂（ICI）治疗与不良事件（AEs）相关，这些事件可能取决于 ICI 剂量。通过应用基于模型的荟萃分析来评估 2005 年至 2018 年发表的临床试验的安全性数据，我们分析了 ICI 治疗相关不良事件（trAE）和免疫介导的不良事件（imAE）发生率的剂量/暴露依赖性。与 PD-1 抑制剂单药治疗不同，CTLA-4 抑制剂单药治疗对评估的大多数 AE 类型表现出剂量/暴露依赖性。此外，PD-1 抑制剂联合治疗显著增强了 trAE 和 imAE 发生率对 CTLA-4 抑制剂剂量/暴露的依赖性。
