Lenvatinib for Hepatocellular Carcinoma: A Literature Review

Abstract

Lenvatinib, which is an oral multikinase inhibitor, showed non-inferiority to the sorafenib in terms of overall survival (OS) and a higher objective response rate (ORR) and better progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). A good liver function and Barcelona Clinic Liver Cancer (BCLC) intermediate stage were the key factors in achieving therapeutic efficacy. The management of adverse events plays an important role in continuing lenvatinib treatment. While sequential therapies contributed to prolonging overall survival, effective molecular targeted agents for the administration after lenvatinib have not been established. Repeated transcatheter arterial chemoembolization (TACE) was associated with a decline in the liver function and poor therapeutic response in BCLC intermediate patients. Recently, the Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement proposed the criteria for TACE unsuitability. Upfront systemic therapy may be better for the BCLC intermediate stage HCC patients with a high tumor burden, while selective TACE will be recommended for obtaining a curative response in patients with a low tumor burden. This article reviews the therapeutic response, management of adverse events, post-progression treatment after Lenvatinib, and treatment strategy for BCLC intermediate stage HCC.

Network Pharmacology-Based Strategy to Investigate the Mechanisms of Lenvatinib in the Treatment of Hepatocellular Carcinoma

“…Lenvatinib is an oral multitarget tyrosine kinase inhibitor (TKI) that has been demonstrated to exhibit potent antiangiogenic and tumor growth inhibitory activity in the treatment of a variety of solid tumors and approved as a monotherapy or combination therapy for differentiated thyroid, hepatocellular carcinoma, and renal cell carcinoma [18]. As a new first-line therapeutic agent in recent ten years, lenvatinib shows no inferior to sorafenib in overall survival (OS), progressive-free survival (PFS), and objective response rate (ORR) [10]. A recent open-label multicenter study showed that patients with unresectable HCC who responded to lenvatinib had a median overall survival time of 22 months [19].…”

“…Despite mounting real-world evidence, there have been few reports of comprehensive findings on lenvatinib therapy for HCC. Meanwhile, some issues about pharmacological mechanisms included in HCC treatment by lenvatinib remain unresolved [10].…”

Transarterial Chemoembolization for Hepatocellular Carcinoma: Why, When, How?

“…Nevertheless, several newer agents have been established over the years, replacing sorafenib as the only systemic therapy available. Lenvatinib is another oral multikinase inhibitor proven to be non-inferior to sorafenib in terms of overall survival for patients with advanced HCC [ 68 ]. Lenvatinib has also showed statistically significant improvement in progression-free survival, objective response rate and time to progression [ 69 ].…”

Improving Outcomes of Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma: New Data and Ongoing Trials

“…A recent study compared the median PFS in TACE-refractory patients that were treated with lenvatinib (5.8 months), sorafenib (3.2 months), and TACE (2.4 months). This indicates treatment with lenvatinib in replacement of TACE has the potential to acquire good therapeutic responses while preserving normal liver function (20). In terms of combination therapies, lenvatinib plus pembrolizumab (an anti-PD-1 antibody) showed encouraging results with improved ORR and DCR for unresectable HCC (NCT03006926, Table 2) (21).…”