The evolving role of lenvatinib at the new era of first-line hepatocellular carcinoma treatment

Abstract

Emergence of multi-targeted kinase inhibitors (MTIs) and immune checkpoint inhibitors (ICI) have changed the landscape of management in hepatocellular carcinoma (HCC). Combination therapy involving ICI has superseded sorafenib as the first-line treatment option for advanced HCC due to their superior response rates and survival benefits based on recently published phase III trials. However, the role of first-line lenvatinib remains uncertain as no prospective trials have compared its efficacy with ICI in advanced HCC. Several retrospective studies have shown that first-line lenvatinib may not be inferior to ICI combination. Indeed, a growing body of evidence suggests that ICI treatment is associated with inferior treatment outcome in non-viral HCC patients, questioning the supremacy of ICI treatment in all patients and rendering first-line lenvatinib as a potential preferred treatment option. Furthermore, in high-burden intermediate-stage HCC, accumulating evidence supports first-line lenvatinib, or in combination with transarterial chemoembolization (TACE), as a preferred treatment option over TACE alone. In this Review, we describe the latest evidence surrounding the evolving role of first-line lenvatinib in HCC.

Consistent efficacy of hepatic artery infusion chemotherapy irrespective of PD‑L1 positivity in unresectable hepatocellular carcinoma

“…Comparable OS and PFS between lenvatinib and HAIC have also been reported by Lee et al ( 29 ). It is worth noting that lenvatinib has been reported to have similar efficacy to first-line atezolizumab/bevacizumab, particularly in specific cases, such as patients with autoimmune disease or other patients receiving immunosuppressants ( 30 , 31 ). Comparable OS and PFS were also previously reported between atezolizumab/bevacizumab and HAIC ( 32 ).…”

Protein and metabolic profiles of tyrosine kinase inhibitors co-resistant liver cancer cells

“…Sorafenib and lenvatinib, both belonging to the class of tyrosine kinase inhibitors (TKIs), serve as molecularly targeted drugs for the treatment of HCC. Their primary focus is on suppressing multiple crucial targets involved in tumor angiogenesis, signal transduction pathways, and immune regulation ( Chan and Chan, 2023 ; Villarruel-Melquiades et al, 2023 ). Sorafenib and lenvatinib effectively restrain the advancement of HCC by impeding an assortment of receptor tyrosine kinases (RTKs) ( Faivre et al, 2020 ).…”

The Position of Multikinase Inhibitors in the Era of Immune-Checkpoint Inhibitors for Hepatocellular Carcinoma

“…Considering the current landscape of immune-checkpoint inhibitors for advanced-stage HCC, it is imperative to reassess the position of multikinase inhibitors like sorafenib or lenvatinib. 8 Firstly, Yoo et al 9 conducted a multinational, multicenter retrospective cohort study to examine the clinical outcomes of multikinase inhibitors as a second-line regimen following progression on Ate/Bev regimen. Among 49 patients in the study, 59.2% utilized sorafenib, 38.8% used lenvatinib, and 1% used cabozantinib as subsequent therapy.…”