Lenvatinib as First-line Treatment of Hepatocellular Carcinoma in Patients with Impaired Liver Function in Advanced Liver Cirrhosis: Real World Data and Experience of a Tertiary Hepatobiliary Center

Abstract

Background and Aims: Lenvatinib is a multikinase inhibitor approved for systemic first line treatment of hepatocellular cancer (HCC) in patients with compensated liver cirrhosis (LC) and unaltered liver function. We aimed to evaluate the efficiency and tolerability of lenvatinib in patients with HCC in a real world setting, also including patients with advanced LC and impaired liver function.
 Methods: Retrospectively, 35 patients with HCC BCLC stages B, C and D were screened. After drop-out and exclusion of patients not receiving active treatment for > 2 weeks, 28 patients (27 male; median age 64.7) with advanced HCC and LC were included in the analysis.
 Results: Fourteen patients (male, median age 62.7) treated had Child-Pugh class B LC, while the other 12 patients had a good liver function Child-Pugh class A (male, median age 68.8). Two patients had advanced Child-Pugh class C LC. The patients received an escalating dosing scheme of lenvatinib up to 12 mg/d. The tolerability of lenvatinib was similar in most of the patients, with no significant difference between the subgroups. Median survival was better in patients with Child-Pugh A LC (p=0.003). More than 60% of the patients with Child-Pugh A were still on treatment at the time of data analysis with a median follow-up of 274 ± 117.5 days compared with 153 days (95%CI: 88.3 – 217.7) in patients with Child-Pugh B and 30 days in Child-Pugh C. The survival benefit correlated significantly with less impaired liver function (p=0.003).
 Conclusion: Tolerability and toxicity of lenvatinib are similar in patients withChild-Pugh class A and class B LC, but patients with less impaired liver function have a better survival benefit.

The prediction of early progressive disease in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab

“…Those reports have been well documented in not only retrospective studies, but also in analyses of the phase-III trials of sorafenib, cabozantinib, ramucirumab, or regorafenib in advanced HCC. [25][26][27][28][29] In the present study, worsening of the ALBI score with atezolizumab plus bevacizumab was observed in both non-e-PD and e-PD patients. In both groups, the ALBI score increased significantly during the first 3 weeks of treatment and did not change thereafter.…”

“…The result is similar to the past reports which showed the prognostic impact of liver function in HCC. Those reports have been well documented in not only retrospective studies, but also in analyses of the phase‐III trials of sorafenib, cabozantinib, ramucirumab, or regorafenib in advanced HCC 25–29 …”

Liver Function and Bleeding Complications Associated with Lenvatinib

“…The study conducted by Cosma et al [7] reported that the differences between the Child-Pugh scores at the beginning and end of therapy were not statistically significant. However, Hatanaka et al [8] reported that the liver function deteriorated from Child-Pugh class A to class B in 43 of the 110 patients (39.1%) following the administration of lenvatinib.…”

“…Although a small number of cases were considered in the retrospective study conducted by Komatsu et al [6], there were no significant differences in the pharmacokinetics, safety, and tolerability of lenvatininb between patients with Child-Pugh class B liver function impairment and patients with Child-Pugh class A liver function [6]. In this issue of the Journal of Gastrointestinal and Liver Diseases, retrospective study by Cosma et al [7] revealed that the tolerability and toxicity of lenvatinib were similar between patients with Child-Pugh class A liver function and patients with Child-Pugh class B liver function impairment. The study reported the same results as those obtained by Komatsu et al [6].…”

Efficacy and safety comparison between Lenvatinib and Sorafenib in hepatocellular carcinoma treatment: a systematic review and meta-analysis of real-world study

“…Three single-arm real studies [13,15,21] and four comparison studies [22][23][24]26] reported median PFS. In the meta-analysis including single-arm real studies (Fig.…”