Systemic treatment for unresectable hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is most commonly found in the context of liver cirrhosis and, in rare cases, in a healthy liver. Its prevalence has risen in recent years, particularly in Western nations, due to the increasing frequency of non-alcoholic fatty liver disease. Advanced HCC has a poor prognosis. For many years, the only proven therapy for unresectable HCC (uHCC) was sorafenib, a tyrosine kinase inhibitor. Recently, the synergistic effect of an immune checkpoint inhibitor, atezolizumab, and bevacizumab outperformed sorafenib alone in terms of survival, making it the recommended first-line therapy. Other multikinase inhibitors, lenvatinib and regorafenib, were also recommended as first and second-line drugs, respectively. Intermediate-stage HCC patients with retained liver function, particularly uHCC without extrahepatic metastasis, may benefit from trans-arterial chemoembolization. The current problem in uHCC is selecting a patient for the best treatment while considering the preexisting liver condition and liver function. Indeed, all study patients had a Child-Pugh class A, and the best therapy for other individuals is unknown. Additionally, in the absence of a medical contraindication, atezolizumab could be combined with bevacizumab for uHCC systemic therapy. Several studies are now underway to evaluate immune checkpoint inhibitors in combination with anti-angiogenic drugs, and the first findings are encouraging. The paradigm of uHCC therapy is changing dramatically, and many obstacles remain for optimum patient management in the near future. The purpose of this commentary review was to give an insight into current systemic treatment options for patients with uHCC who are not candidates for surgery to cure the disease.

Keywords: Hepatocellular carcinoma; Unresectable hepatocellular carcinoma; Non-alcoholic fatty liver disease; Tyrosine kinase inhibitor; Sorafenib; Lenvatinib; Immune checkpoint inhibitor; Atezolizumab; Bevacizumab

Core Tip: Hepatocellular carcinoma (HCC) is a major health problem that is the fourth leading cause of cancer-related mortality worldwide. The 5-year survival rate was nearly 19%, but only 2% in metastatic HCC. The first oral multikinase inhibitor for the systemic treatment of advanced or unresectable HCC (uHCC) was sorafenib. However, when compared to sorafenib, the combination of atezolizumab and bevacizumab increased survival rates and was authorized as first-line treatment for uHCC. Regorafenib and cabozantinib are suggested for use as second-line drugs in the event that the disease progresses. Transarterial chemoembolization for palliative care or downstaging is also suggested. This review focused on systemic therapy for uHCC patients who are not appropriate for liver-directed therapy.