Systemic Therapy for Advanced Hepatocellular Carcinoma: Current Stand and Perspectives

SIMPLE SUMMARY: Hepatocellular carcinoma is an aggressive disease with a poor prognosis. Treatment options for advanced disease have changed substantially in the last few years with the development of targeted therapy, immunotherapy and combinations of both treatment options. This development has led to an increase in disease control and overall survival. The aim of this review article is to summarize the current treatment options and future perspectives on the treatment of advanced hepatocellular carcinoma. ABSTRACT: Hepatocellular carcinoma often develops in the context of chronic liver disease. It is the sixth most frequently diagnosed cancer and the third most common cause of cancer-related mortality worldwide. Although the mainstay of therapy is surgical resection, most patients are not eligible because of liver dysfunction or tumor extent. Sorafenib was the first tyrosine kinase inhibitor that improved the overall survival of patients who failed to respond to local therapies or had advanced disease, and for many years, it was the only treatment approved for the first-line setting. However, in recent years, trials have demonstrated an improvement in survival with treatments based on immunotherapy and new targeting agents, thereby extending the treatment options. A phase III trial showed that a combination of immunotherapy and targeted therapy, including atezolizumab plus bevacizumab, improved survival in the first-line setting, and is now considered the new standard of care. Other agents and combinations are being tested, including the combination of nivolumab plus ipilimumab and tremelimumab plus durvalumab, and they reportedly have clinical benefits. The aim of this manuscript is to review the latest approved therapeutic options in first- and second-line settings for advanced HCC and discuss future perspectives.