Lenvatinib as a therapy for unresectable hepatocellular carcinoma

ABSTRACT

Introduction: Since 2007 Sorafenib has represented the only approved drug for first-line treatment of advanced hepatocellular carcinoma (HCC). Lenvatinib, an orally active inhibitor of multiple receptor tyrosine kinases (VEGFR 1–3, FGFR 1–4, PDGFRa, RET and KIT), showed preclinical and clinical activity in the treatment of solid tumors, including HCC.

Areas covered: In this review, we summarize the current therapeutic paradigm for the systemic treatment of advanced HCC, focusing on Lenvatinib pre-clinical and clinical development. Keywords ‘Lenvatinib’, ‘ Target therapy’, ‘REFLECT trial’, ‘Hepatocellular carcinoma’, ‘HCC’, ‘Sorafenib’ were used for literature search on PubMed.

Expert commentary: In Phase-III multicentric REFLECT trial Lenvatinib demonstrated a non-inferior overall survival (OS) compared to Sorafenib in the first-line treatment of advanced HCC, with a manageable toxicity profile, becoming a valid alternative option in the therapeutic repertoire of this disease. Nevertheless, the potential role of Lenvatinib in real-life clinical practice has still to be defined, especially in the light of the positive results that have been achieved with other new therapeutic agents (e.g. immunotherapy).

KEYWORDS:

• Lenvatinib
• hepatocellular carcinoma
• REFLECT trial
• target therapy
• Sorafenib

Information resources

• Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. The New England journal of medicine, 359(4), 378–390 (2008).

• Ikeda K, Kudo M, Kawazoe S et al. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. Journal of gastroenterology, 52(4), 512–519 (2017).

• Kudo M, Finn RS, Qin S et al. Lenvatinib versus Sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet, (2018).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Notes on contributors

All authors conceived and designed the manuscript. All authors analyzed and interpreted the data, and drafted the article. All authors revised it critically for important intellectual content and finally approved the version to be submitted.

Additional information

Funding

This manuscript was not funded