Systemic therapy of liver cancer

Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis. More than 80% of patients are diagnosed at an advanced stage, and most patients with HCC also have liver cirrhosis that complicates cancer management. No targeted treatment options currently exist outside genomics-based clinical trials. Multiple tyrosine kinase inhibitors (mTKIs) such as sorafenib, lenvatinib, cabozantinib, and regorafenib have been used to treat advanced hepatocellular carcinoma (aHCC). Immune checkpoint inhibitors including nivolumab and pembrolizumab have shown survival benefit. More recently, atezolizumab in combination with bevacizumab resulted in improved overall survival and progression-free survival, compared with sorafenib in patients with aHCC in the first-line setting. The combination of nivolumab with ipilimumab as an alternative in the treatment of patients treated with sorafenib has inspired various combination studies of immune checkpoint inhibitors. Currently, ongoing studies of systemic therapy consist of various immune-based combination therapies. Finally, there is no established adjuvant and neoadjuvant therapy although a few early phase studies show promising results. In this chapter, we summarize current approaches of systemic treatment in patients with liver cancer.