Lenvatinib plus immune checkpoint inhibitors or locoregional therapy in unresectable hepatocellular carcinoma: Lessons learned and moving forwards

Hepatocellular carcinoma is one of the deadliest neoplasms around the world, and a major proportion of patients are diagnosed in an advanced state not amenable to curative treatment. Lenvatinib, a promising first-line targeted therapy, has shown antitumour activity in both preclinical studies and clinical trials. Emerging evidence indicates that a combination of lenvatinib plus anti-PD-1 inhibitors or locoregional therapies exerts a stronger antitumour effect than monotherapy and even offers the possibility of long-term survival while maintaining acceptable tolerability. Several studies have also shown the superiority of lenvatinib over sorafenib in combination strategies. This review addresses the rationale behind lenvatinib-based combination therapies and comprehensively summarizes various clinical studies investigating lenvatinib in combination with immune checkpoint inhibitors (ICIs), locoregional therapies, and other systemic treatments. We discuss the unsatisfactory search for suitable biomarkers and key ongoing trials in this field.