Milestones in the treatment of hepatocellular carcinoma: A systematic review

Crit Rev Oncol Hematol. 2021 Jan:157:103179. doi: 10.1016/j.critrevonc.2020.103179. Epub 2020 Nov 18.


According to data provided by WHO (World Health Organization), hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide. Since the approval of sorafenib in 2008, several trials have assessed other particles for the treatment of HCC, but few have proven to be effective. ESMO (European Society for Medical Oncology) guidelines have been changed several times recently. This systematic review aims to describe both successful and failed trials of systemic treatments for HCC. Methods: We examined randomized, phase III trials of first- and second-line treatments in adults, identifying 23 fully-published trials and 2 reported as abstracts. The latest advances in immunotherapy were also briefly discussed. Conclusions: The landscape of HCC treatment has changed significantly in recent years. Several small molecule inhibitors currently form the core of HCC treatment; however, immunotherapy is now emerging as a promising treatment option.

Keywords: hepatocellular carcinoma; immunotherapy; liver cancer; sorafenib; systemic treatment.

Publication types

  • Systematic Review

MeSH terms

  • Carcinoma, Hepatocellular* / therapy
  • Humans
  • Immunotherapy
  • Liver Neoplasms* / therapy
  • Sorafenib / therapeutic use


  • Sorafenib