Association of lenvatinib plasma concentration with clinical efficacy and adverse events in patients with hepatocellular carcinoma

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.