Exploratory analysis of target concentration of lenvatinib in the treatment of hepatocellular carcinoma
Exploratory analysis of target concentration of lenvatinib in the treatment of hepatocellular carcinoma
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DOI：
10.1007/s00280-021-04286-2
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发表时间：
2021-04-29
影响因子：
3
通讯作者：
Terada, Tomohiro
中科院分区：
文献类型：
--
作者：
Noda, Satoshi;Iida, Hiroya;Terada, Tomohiro
目的 我们旨在通过确定肝细胞癌 (HCC) 患者的目标谷浓度来评估乐伐替尼的暴露毒性/疗效关系。方法 在这项回顾性观察性研究中，纳入了 2018 年 8 月至 2020 年 4 月期间接受乐伐替尼治疗的 28 名 HCC 患者。我们评估了乐伐替尼谷浓度与 3 级以上毒性发生之间的关联。此外，我们还估计了乐伐替尼谷浓度与应答者状态（疾病控制；完全应答、部分应答或疾病稳定）和无进展生存期（PFS）的关联。结果 ≥ 3 级毒性组 (n = 15) 的平均乐伐替尼谷浓度显着高于≥ 3 级毒性组，应答者状态为 71.4 ng/mL [曲线下面积 (AUC) 0.86，95% 置信区间 (CI) 0.71-1.00； p < 0.05] 和 36.8 ng/mL（AUC 0.95，95% CI 0.85-1.00；p < 0.05）。乐伐替尼浓度为 36.8-71.4 ng/mL 的 PFS 比浓度 < 36.8 ng/mL 和≥ 71.4 ng/mL 的 PFS 更长[中位值分别为 13.3 个月 (36.8-71.4 ng/mL) vs. 3.5 个月 (< 36.8 ng/mL) 和 7.8 个月 (>= 71.4 ng/mL)]。结论 考虑到这些结果，我们建议乐伐替尼治疗 HCC 时的目标谷浓度为 36.8-71.4 ng/mL，以维持疾病控制状态并降低 3 级以上毒性。
Purpose We aimed to evaluate exposure-toxicity/efficacy relationship of lenvatinib by determining its target trough concentration for patients with hepatocellular carcinoma (HCC). Methods In this retrospective, observational study, 28 HCC patients who had been treated with lenvatinib were enrolled between August 2018 and April 2020. We evaluated the association between the trough lenvatinib concentration and occurrence of grade >= 3 toxicities. Additionally, we estimated the association of the trough lenvatinib concentration with responder status (disease control; complete response, partial response, or stable disease), and progression-free survival (PFS). Results The mean trough lenvatinib concentration was significantly higher in the group with grade >= 3 toxicity (n = 15) than in the group with grade = 3 toxicities and responder status were 71.4 ng/mL [area under the curve (AUC) 0.86, 95% confidence interval (CI) 0.71-1.00; p < 0.05] and 36.8 ng/mL (AUC 0.95, 95% CI 0.85-1.00; p < 0.05), respectively. Lenvatinib concentrations of 36.8-71.4 ng/mL resulted in longer PFS than concentrations < 36.8 ng/mL and >= 71.4 ng /mL [median 13.3 months (36.8-71.4 ng/mL) vs. 3.5 months (< 36.8 ng/mL) and 7.8 months (>= 71.4 ng /mL), respectively]. Conclusions Considering these results, we propose that the target trough concentration of lenvatinib could be 36.8-71.4 ng/mL for maintaining disease control status and reducing grade >= 3 toxicity in the treatment of HCC.