Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients With Unresectable Advanced or Recurrent NSCLC: An Exploratory Study of J-TAIL

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Abstract

Introduction

This study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg once every three weeks regimen.

Methods

A subgroup of 262 of 1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August 2018 to October 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles 1 to 4, their association with effectiveness, and the association between atezolizumab maximum plasma concentrations (Cmax) calculated using the existing PopPK model and AEs of special interest (AESIs).

Results

Overall, 175 of 262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (Eastern Cooperative Oncology Group performance status ≥ 2, 12.0%; age ≥ 75 y, 28.9%; atezolizumab as more than or equal to third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 versus Q2 to Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated Cmax at cycle 1 increased.

Conclusions

In real-world Japanese patients with unresectable advanced/recurrent NSCLC, PKs were similar to previous reports. Certain patient populations had shorter overall survival, and atezolizumab plasma concentrations in cycle 3 were lower in this population. Elevated Cmax at cycle 1 may be associated with an increased frequency of AESIs.

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不可切除的晚期或复发性非小细胞肺癌患者使用阿特珠单抗的真实世界药代动力学、有效性和安全性:J-TAIL 探索性研究
简介:本研究使用已建立的群体PK(PopPK)模型验证了日本NSCLC患者使用阿特珠单抗的真实药代动力学(PK)数据,并探讨了每三周一次1200毫克治疗方案的PK参数、疗效和不良事件(AEs)之间的关系。方法来自J-TAIL的1039名患者中的262名患者同意参加这项探索性研究,对阿特珠单抗单药治疗不可切除的晚期/复发性NSCLC进行PK评估(2018年8月至2019年10月;197家机构)。我们评估了阿特珠单抗第三周期输注开始前的血浆浓度(分为1至4分位)、其与疗效的关系,以及使用现有PopPK模型计算的阿特珠单抗最大血浆浓度(Cmax)与特殊关注AEs(AESIs)之间的关系。结果262例患者中共有175例入选;基线特征与J-TAIL入选患者相似(东部合作肿瘤学组表现状态≥2,占12.0%;年龄≥75岁,占28.9%;阿替佐珠单抗大于或等于三线治疗,占57.5%)。阿特珠单抗的血浆浓度与之前报道的日本/非日本患者的数据相似。第一季度与第二至第四季度相比,阿特珠单抗血浆浓度较低的患者总生存期明显缩短,但无进展生存期保持不变。PK数据完全符合PopPK模型,随着第1周期计算Cmax的增加,AESI的发生频率也随之增加。某些患者的总生存期较短,而这些患者在第3周期的阿特珠单抗血浆浓度较低。第1周期Cmax升高可能与AESI频率增加有关。
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来源期刊
CiteScore
4.20
自引率
0.00%
发文量
145
审稿时长
19 weeks
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