Updates on clinical trials for the management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is the leading cause of death in patients with cirrhosis and the fourth most common cause of cancer-related mortality in the world. In the recent years, we have seen the emergence of promising therapies for the treatment of HCC. Locoregional therapies including surgical resection, liver transplant, Image-guided ablation, and chemoembolization have survival benefits in early disease limited to liver, however each modality has its own limitations. Unfortunately, most of the patients are diagnosed in advance stage of disease requiring systemic management. Sorafenib has been the mainstay of treatment for a decade until the introduction of lenvatinib, which is noninferior to sorafenib. Finally, survival benefit of regorafenib in HCC patients who progress on sorafenib has heralded a new era of second-line treatment, quickly followed by ramucirumab, cabozantinib, and immune checkpoint inhibitors (ICIs). Combination therapies with ICIs and targeted agents in conjunction with locoregional therapies have shown promise paving the way for further clinical trials. Effort is needed to develop additional novel therapies to potentially augment the current standard treatments as well as to understand the underlying drug resistance mechanisms and prognostic parameters in order to improve survival in patients with HCC.