Lenvatinib: A Potential Breakthrough in Advanced Hepatocellular Carcinoma?

Treatment of advanced hepatocellular carcinoma (HCC) has reached a plateau after the approval of sorafenib in 2007. Several molecularly targeted therapies have failed to show significant improvement in survival outcomes compared with sorafenib, due to flaws in the design of clinical trials or failure to understand and correct for the competing co-morbidity of liver dysfunction. Lenvatinib is a multitargeted tyrosine kinase inhibitor with potent antiangiogenic effects, and has recently been approved for differentiated thyroid cancer. Lenvatinib has shown highly promising response data in Phase I/II clinical trials in HCC, although with some concerns regarding its toxicity profile. The pivotal Phase III REFLECT trial comparing lenvatinib to sorafenib has been completed, and the results of this trial will determine whether lenvatinib represents a breakthrough in the current crisis affecting HCC drug development.