BACKGROUND: Prognosis is very poor for advanced HCC patients partially due to 
lack of effective systemic treatment. Sorafenib was the only approved agent for 
advanced HCC since 2007 until recent breakthroughs. In this article, we will 
review the newer approved and promising agents in the treatment of advanced HCC 
in the first line setting and beyond progression.
MAIN BODY: The Food and Drug Administration approved sorafenib as it 
demonstrated 3 months overall survival benefit compared to placebo in the first 
line setting over 10 years ago. Multiple single agent and combination therapies 
have been studied but failed to show benefit. Chemotherapy has limited role in 
patients with advanced HCC given poor hepatic reserve due to underlying 
cirrhosis. A new era of treatment for advanced HCC arrived recently with 
exciting data presented for lenvatinib, regorafenib, cabozantinib, nivolumab, 
ramucirumab and several other promising clinical trials.
CONCLUSION: Advanced HCC patients are difficult to treat with poor outcomes. 
After initial approval of sorafenib in 2007, we recently have multiple new 
agents that showed benefit and promising activity, and are set to change the 
landscape of HCC treatment.