Lenvatinib as a therapy for unresectable hepatocellular carcinoma

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).