Evaluation of the therapeutic effects and tolerability of modified lenvatinib administration methods for unresectable hepatocellular carcinoma: A preliminary study

Abstract

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor, is a standard therapeutic agent for hepatocellular carcinoma, but the high incidence of adverse events (AEs) related to LEN treatment often necessitates treatment discontinuation. The present study aimed to clarify the therapeutic efficacy and tolerability of modified LEN dosing methods, such as alternate-day dosing, necessitated by AEs of LEN. A total of 66 patients who received LEN at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and January 2022 were retrospectively evaluated. These patients were divided into those who completed treatment with the standard administration method (standard LEN, n=48) and those who changed from the standard administration method to a modified administration method in the middle of treatment [modified LEN (weekends off/alternate days), n=18]. The treatment duration and reasons for discontinuation of LEN treatment were analysed. The discontinuation rate due to AEs in the modified LEN group (1 patient) was less compared with that in the standard LEN group (16 patients) (P=0.022). The median treatment duration for patients in the standard LEN (n=48), modified LEN (weekends off, n=6) and modified LEN (alternate days, n=12) groups was 71 [95% confidence interval (CI) 55-134], 483 (95% CI: 193-644) and 222 (95% CI: 98-303) days, respectively (P=0.044). Modification of the administration method ensured fewer AE-related treatment discontinuations. However, weekends off dosing showed a longer treatment duration compared with standard dosing, whereas alternate day dosing showed no difference from standard dosing.

Evaluation of Atezolizumab Plus Bevacizumab Versus Modified Lenvatinib Therapy in Child-Pugh A Unresectable Hepatocellular Carcinoma

“…This may be because only two of the 11 patients in the modified LEN group received the weekends-off regimen. In the report by Kimura et al, the treatment duration with the weekendsoff method was longer than that with the standard LEN method, whereas the duration with the alternate-day method was equivalent to that with the standard LEN method (14).…”

“…The survival curves of the Atez/BV and LEN groups in this study were not significantly different and tended to overlap. Some studies have investigated the effect of modifying the administration method for LEN on its therapeutic effects (13,14). Iwamoto et al reported that the treatment period and duration of survival for LEN were significantly prolonged with the weekends-off administration method compared to those with the standard administration method (13).…”

“…Iwamoto et al reported that the treatment period and duration of survival for LEN were significantly prolonged with the weekends-off administration method compared to those with the standard administration method (13). Kimura et al also showed that the weekends-off method allowed for a longer treatment duration than the alternate-day or standard LEN methods (14). Therefore, it was expected that using LEN with a better administration method would result in longer treatment duration and OS than those with Atez/BV.…”

“…Unfortunately, in this study, most results related to LEN were associated with the alternate-day regimen, and there is a possibility that the difference in treatment duration with the weekends-off regimen would be significant, which should be considered in future studies. This is because the weekends-off regimen was associated with a longer treatment duration than the alternate-day and standard regimens (14). Moreover, in this study, we compared Atez/BV and LEN as first-line treatments, but it is hoped that appropriate LEN administration methods for subsequent lines of therapy are considered in future studies, especially given that the usefulness of LEN after Atez/BV treatment has been previously demonstrated (19,20).…”

“…Some studies have investigated whether LEN tolerability and efficacy can be enhanced by modifying the dosing regimen, such as 5 days of drug administration with 2day intervals (weekends-off) and alternate-day administration (13). In particular, the weekends-off method allowed for a longer treatment duration than the alternate-day or the standard LEN regimens (14). Therefore, LEN with a better administration method may be superior to Atez/BV in terms of treatment duration and OS.…”