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) 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).

RESULTS

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).

CONCLUSION

Maintaining C above 42.68 ng/mL was crucial for achieving the ORR in patients with HCC.