Systemic therapy for hepatocellular carcinoma: current status and future perspectives

Abstract Since sorafenib was established as the standard of care for patients with advanced hepatocellular carcinoma, various tyrosine kinase inhibitors, targeting vascular endothelial growth factor receptor and other molecular growth factors, have been developed. Lenvatinib demonstrated non-inferiority to sorafenib in terms of the overall survival, and it has also become confirmed as another standard of care for patients with advanced hepatocellular carcinoma. Recently, various immune checkpoint inhibitors have been investigated, either as monotherapy or in combination with another agent, and superiority of the combination of atezolizumab plus bevacizumab, in terms of the overall survival and progression-free survival, has been demonstrated over sorafenib, which is recognized as the treatment regimen of first choice for first-line systemic therapy of advanced hepatocellular carcinoma. Regorafenib, cabozantinib and ramucirumab have been demonstrated to show survival benefits as second-line treatment agents for progressive disease after first-line sorafenib treatment. There are still various medical requirements in systemic therapy for hepatocellular carcinoma. To date, no evidence has been established for the selection of sequential treatment after immune checkpoint inhibitor-containing treatments, especially atezolizumab plus bevacizumab. A promising treatment for Child-Pugh class B hepatocellular carcinoma patients is also an urgent medical need that has not yet been met. Although there are some difficulties in establishing the needed evidence, well-designed clinical trials are warranted.