Optimal sequence of systemic therapy after sorafenib failure in patients with hepatocellular carcinoma

摘要

Hepatocellular carcinoma (HCC) is one of the solid cancers with a dismal prognosis, particularly when it is diagnosed in the unresectable/advanced stage [ ]. Owing to the increasing incidence of HCC in developed countries over the last decade [ ], there has been a remarkable progress in the development of novel drugs for systemic treatment, enabling HCC to escape from being classified as an “orphan tumor.” Indeed, several tyrosine kinase inhibitors, including sorafenib, lenvatinib, regorafenib, and cabozantinib, have been approved as first- or second-line systemic therapies for patients with unresectable HCC [ - ]. Furthermore, nivolumab, which is a immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1) on cytotoxic T cells, and ramucirumab, a monoclonal antibody inhibiting vascular endothelial growth factor receptor 2 (VEGFR2), have been approved as second-line systemic therapies with an action mechanism different from that of tyrosine kinase inhibitors [ , ]. With various systemic therapeutic options now available, liver specialists treating patients with HCC have to answer a new question: what is the optimal second-line systemic treatment option after sorafenib failure?