Correlation between nivolumab exposure and treatment outcomes in non-small-cell lung cancer
Correlation between nivolumab exposure and treatment outcomes in non-small-cell lung cancer
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DOI：
10.1016/j.ejca.2018.12.008
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发表时间：
2019-03-01
影响因子：
8.4
通讯作者：
Mathijssen, Ron H. J.
中科院分区：
文献类型：
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作者：
Basak, Edwin A.;Koolen, Stijn L. W.;Mathijssen, Ron H. J.
简介：纳武利尤单抗治疗在疗效和毒性方面存在较大的患者间差异，这可能部分由纳武利尤单抗暴露的差异解释。尚未对nivolumab在常规医疗保健中的暴露-反应关系进行广泛研究。因此，我们旨在确定nivolumab治疗的非小细胞肺癌（NSCLC）患者中可能的疗效-反应关系。方法：纳入2016年5月5日至2017年8月1日期间开始二线nivolumab治疗（3 mg/kg Q2 W）的NSCLC患者，并前瞻性收集其系列血液样本，毒性数据和结局数据。随访至2017年11月1日。根据基于实体瘤疗效评价标准v1.1的最佳总体缓解（BOR）和根据不良事件通用术语标准的毒性对患者进行分类。在治疗2、4和10周后测量纳武单抗谷浓度，不包括给药延迟，并分别使用方差分析和独立样本t检验相对于BOR或毒性检验计算的几何平均值。总生存期（OS）和无进展生存期之间进行了比较高，低谷浓度groups.Results：76例患者进行了分析。应答者（n = 15）的平均谷浓度高于进展患者（n = 33）：2周后高47%（p = 0.001），4周后高53%（p = 0.008），10周后高73%（p = 0.002）。更高的谷浓度与更长的OS相关（p = 0.001）。结论：本研究显示，对nivolumab有反应的NSCLC患者比进展患者具有更高的nivolumab暴露，表明潜在的治疗-反应关系。进一步的临床研究应集中于阐明这些疗效-反应关系。(C)2018爱思唯尔有限公司版权所有
Introduction: Nivolumab treatment is subject to large interpatient variability in both efficacy and toxicity, which may partly be explained by differences in nivolumab exposure. Exposure-response relationships in regular healthcare have not been extensively investigated for nivolumab. Therefore, we aimed to identify possible exposure-response relationships in nivolumab-treated patients with non-small-cell lung cancer (NSCLC).Methods: Patients with NSCLC who started second-line nivolumab therapy (3 mg/kg Q2W) between May 5th 2016 and August 1st 2017, and from whom serial blood samples, toxicity data and outcome data were prospectively collected, were included. Follow-up was carried out until November 1st 2017. Patients were classified according to the best overall response (BOR) based on the Response Evaluation Criteria in Solid Tumours, v1.1, and toxicities according to the Common Terminology Criteria for Adverse Events. Nivolumab trough concentrations were measured after 2, 4 and 10 weeks of treatment, excluding dose delays, and calculated geometric means were tested versus BOR or toxicity using analysis of variance and an independent samples t-test, respectively. Overall survival (OS) and progression-free survival were compared between high and low trough concentration groups.Results: Seventy-six patients were evaluable for analyses. Responders (n = 15) had higher mean trough concentrations than patients with progression (n = 33): 47% higher after 2 weeks (p = 0.001), 53% higher after 4 weeks (p = 0.008) and 73% higher after 10 weeks (p = 0.002). Higher trough concentrations were associated with longer OS (p = 0.001).Conclusions: This study shows that patients with NSCLC with a response to nivolumab had a higher nivolumab exposure than patients with progression, indicating a potential exposure-response relationship. Further clinical research should focus on clarifying these exposureeresponse relationships. (C) 2018 Elsevier Ltd. All rights reserved.