Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Cancer Chemother Pharmacol. 2020 Dec;86(6):803-813. doi: 10.1007/s00280-020-04178-x. Epub 2020 Oct 23.
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).
Twenty-one patients with HCC who received lenvatinib were enrolled. We examined the median trough concentration (C) of plasma lenvatinib until the first clinical response evaluation. The receiver-operating characteristic curve was drawn to show the discrimination potential of the C 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).
The C 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 group (≥ 42.68 ng/mL) than in the low-C 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 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 group than in the low-C group. Multivariate analysis showed that high-C was significantly associated with ORR development (odds ratio, 15.00; 95% confidence interval, 1.63-138.16; p = 0.0168).
Maintaining C above 42.68 ng/mL was crucial for achieving the ORR in patients with HCC.
本研究旨在探讨肝细胞癌（HCC）患者 lenvatinib 谷浓度与客观缓解率（ORR）和不良事件之间的关系。
纳入 21 例接受 lenvatinib 治疗的 HCC 患者。我们检测 lenvatinib 血浆谷浓度（C），直至首次临床反应评估。使用改良实体瘤反应评价标准（RECIST）绘制受试者工作特征曲线，以显示 C 对 ORR 的鉴别潜力。根据不良事件通用术语标准（第 5.0 版）对不良事件进行分级。
完全缓解和部分缓解组的 C 值明显高于稳定疾病和进展疾病组。高 C 组（≥42.68ng/ml）的 ORR 明显高于低 C 组（<42.68ng/ml）（80.0% vs. 18.2%；p=0.0089）。虽然高、低 C 组大多数不良事件的发生率无差异，但高 C 组任何等级厌食症（100.0% vs. 45.5%；p=0.0124）和 3 级严重高血压（70.0% vs. 18.2%；p=0.0300）的发生率明显高于低 C 组。多变量分析显示，高 C 与 ORR 发展显著相关（优势比，15.00；95%置信区间，1.63-138.16；p=0.0168）。
维持 C 浓度高于 42.68ng/ml 对 HCC 患者获得 ORR 至关重要。
