Association of lenvatinib plasma concentration with clinical efficacy and adverse events in patients with hepatocellular carcinoma
Association of lenvatinib plasma concentration with clinical efficacy and adverse events in patients with hepatocellular carcinoma
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DOI：
10.1007/s00280-020-04178-x
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发表时间：
2020-10-23
影响因子：
3
通讯作者：
Ieiri, Ichiro
中科院分区：
文献类型：
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作者：
Hata, Kojiro;Suetsugu, Kimitaka;Ieiri, Ichiro
目的本研究旨在探讨肝细胞癌患者低谷血药浓度与客观有效率(ORR)及不良事件的关系。方法21例接受雷瓦替尼治疗的肝细胞癌患者入选。我们检测了在第一次临床反应评估之前的血浆Lenvatinib的中低谷浓度(C-谷中值)。在实体瘤中使用改进的反应评估标准，绘制接受者-操作特征曲线，以显示C槽中位数对ORR的区分潜力。根据不良事件通用术语标准对不良事件进行分级。5.0)。结果完全应答组和部分应答组的C-槽中位数明显高于稳定期和进展组。高C低谷中位数组的ORR值(42.68 ng/mL)显著高于低C低谷中位数组(80.0%vs.18.2%；P=0.0089)。尽管高C低谷中位数组和低C低谷中位数组大多数不良事件的发生率没有差异，但高C低谷中位数组任何程度的厌食症(100.0%对45.5%；p=0.0124)和3级严重高血压(70.0%对18.2%；p=0.0300)的发生率显著高于低C低谷中位数组。多因素分析显示，高C低谷中位数与ORR的发生显著相关(优势比，15.00；95%可信区间，1.63-138.16；p=0.0168)。结论维持C-槽中位数在42.68 ng/m L以上是实现肝癌患者ORR的关键。
Purpose This study aimed to examine the association between the trough plasma concentration of lenvatinib with the objective response rate (ORR) and adverse events in patients with hepatocellular carcinoma (HCC). Methods Twenty-one patients with HCC who received lenvatinib were enrolled. We examined the median trough concentration (C-trough median) of plasma lenvatinib until the first clinical response evaluation. The receiver-operating characteristic curve was drawn to show the discrimination potential of the C-trough median for the ORR, using the modified Response Evaluation Criteria in Solid Tumors. Adverse events were graded based on the Common Terminology Criteria for Adverse Events (ver. 5.0). Results The C-trough median values in the complete response and partial response group were significantly higher than those in the stable disease and progressive disease groups. The ORR was significantly higher in the high-C-trough median group (>= 42.68 ng/mL) than in the low-C-trough median group (< 42.68 ng/mL) (80.0% vs. 18.2%; p = 0.0089). Although there was no difference in the occurrence of most adverse events between the high- and low-C-trough median groups, the occurrence of any grade anorexia (100.0% vs. 45.5%; p = 0.0124) and grade 3 serious hypertension (70.0% vs. 18.2%; p = 0.0300) was significantly higher in the high-C-trough median group than in the low-C-trough median group. Multivariate analysis showed that high-C-trough median was significantly associated with ORR development (odds ratio, 15.00; 95% confidence interval, 1.63-138.16; p = 0.0168). Conclusion Maintaining C-trough median above 42.68 ng/mL was crucial for achieving the ORR in patients with HCC.