Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

Abstract

It was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.

PD-1/PD-L1 Immuno-Mediated Therapy in NAFLD: Advantages and Obstacles in the Treatment of Advanced Disease

“…Currently, the only proposed strategies for HCC are loco-regional treatments (i.e., hepatic resection, ablation, transarterial chemoembolisation), inhibitors of tyrosin kinase/anti-angiogenetic agents, as Sorafenib, Regorafenib and ramucirumab, and ultimately liver transplantation [ 50 ]. Very recently also Lenvatinib, an oral multikinase inhibitor, was confirmed as non-inferior to Sorafenib in untreated advanced hepatocellular carcinoma [ 51 , 52 ].…”

Changing the Treatment Paradigm for Hepatocellular Carcinoma Using Atezolizumab plus Bevacizumab Combination Therapy

“…In contrast to ICI, previous studies have reported that lenvatinib is equally effective in NASH-HCC with other etiologies [87] and more effective against NASH/NAFLDassociated HCC than against HCC with alcohol or viral etiologies [88]. Therefore, when a patient is clinically suspected to present NASH-HCC and does not respond to atezolizumab plus bevacizumab therapy, the treatment should be immediately switched to lenvatinib or another therapy associated with improved disease status.…”

Is There Still a Place for Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma at the Time of Immunotherapies? A Focus on Lenvatinib

“…The efficacy of lenvatinib does not appear to be influenced by the etiology of the liver disease. Hiraoka et al recently conducted a multicentre retrospective study with 103 patients with NAFLD and 427 patients with AFLD or viral -related HCC treated by lenvatinib [ 58 ] without significant difference in overall survival (OS) (20.5 vs. 16.9 months, p = 0.057) between viral and NAFLD group.…”