Population Pharmacokinetics of Nivolumab in Japanese Patients with Nonsmall Cell Lung Cancer.
Population Pharmacokinetics of Nivolumab in Japanese Patients with Nonsmall Cell Lung Cancer.
复制标题
DOI：
10.1097/ftd.0000000000000996
复制
发表时间：
2023-02-01
影响因子：
2.5
通讯作者：
Hashida, Tohru
中科院分区：
文献类型：
--
作者：
Tohi, Makiko;Irie, Kei;Mizuno, Tomoyuki;Okuyoshi, Hiroyuki;Hirabatake, Masaki;Ikesue, Hiroaki;Muroi, Nobuyuki;Eto, Masaaki;Fukushima, Shoji;Tomii, Keisuke;Hashida, Tohru
补充数字内容可在正文中找到。Nivolumab是一种抗程序性死亡-1(PD-1)抗体，用于包括非小细胞肺癌(NSCLC)在内的各种癌症的免疫肿瘤学治疗。这项研究的目的是描述NSCLC患者体内nivolumab的真实人群药代动力学(PK)。PK样本是通过对接受nivolumab单一疗法治疗的日本NSCLC患者的机会性抽样收集的。群体PK分析采用非线性混合效应模型中的二室模型。患者特有的因素，如体重、年龄、性别、血清白蛋白、估计的肾小球滤过率、功能状态、肿瘤中程序性细胞死亡受体配体1的表达和治疗时间被评估为潜在的清除协变量。总共收集了34名患者的223份血清样本进行分析。中位年龄69岁(38~83岁)，体重62.7 kg(36.8~80.5 kg)。平均(95%可信区间)清除估计为0.0064 L/小时(0.0058-0.0070 L/小时)。纳入白蛋白水平、估计的肾小球滤过率和治疗周期显著改善了模型拟合度。在日本NSCLC患者中，使用机会性抽样策略开发了一个真实世界的nivolumab人群PK模型。有必要进行进一步的研究，以确定暴露-反应关系的特征，并确定这些患者的最佳剂量方案。
Supplemental Digital Content is Available in the Text. Nivolumab is an antiprogrammed death-1 (PD-1) antibody used for immuno-oncological therapy of various cancers, including nonsmall cell lung cancer (NSCLC). This study aimed to characterize the real-world population pharmacokinetics (PK) of nivolumab in patients with NSCLC. PK samples were collected by opportunistic sampling of Japanese patients with NSCLC treated with nivolumab monotherapy. Population PK analysis was performed using a two-compartment model in Nonlinear Mixed Effect Model. Patient-specific factors such as body weight, age, sex, serum albumin, estimated glomerular filtration rate, performance status, programmed cell death receptor ligand 1 expression in tumors, and treatment periods were evaluated as potential covariates for clearance. A total of 223 serum samples collected from 34 patients were available for analysis. The median (min–max) age and weight were 69 years (38–83 years) and 62.7 kg (36.8–80.5 kg), respectively. The mean (95% confidence interval) clearance estimate was 0.0064 L/h (0.0058–0.0070 L/h). The inclusion of the ALB level, estimated glomerular filtration rate, and treatment period significantly improved the model fit. A real-world nivolumab population PK model was developed using an opportunistic sampling strategy in Japanese patients with NSCLC. Further studies are warranted to characterize the exposure–response relationship and determine the optimal dosing regimens for these patients.