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ESMO E-Learning: Advances in Hepatocellular Carcinoma

Learning objectives

  1. To provide an update on epidemiology, prognostication, staging and treatment algorithms in hepatocellular carcinoma
  2. To provide an update on the progress made in systemic therapy for hepatocellular carcinoma and put evidence from clinical studies into practice perspective  
  3. To summarise current evidence from clinical studies combining transarterial chemoembolisation with systemic therapy for hepatocellular carcinoma
  4. To summarise current evidence from clinical studies on the role of selective internal radiotherapy in the management of hepatocellular carcinoma


In this E-Learning module, the author provides state-of-the-art in terms of epidemiology data, prognostication, staging and treatment algorithms. He summarises evidence from clinical trials with systemic therapy, studies combining transarterial chemoembolisation (TACE) with systemic therapy and outlines the current role of selective internal radiotherapy (SIRT) and future perspective in the management of hepatocellular carcinoma.

Liver cancer is the second most common cause of cancer related mortality. In general, 80-90% of patients with hepatocellular carcinoma have background chronic liver disease.  

Sorafenib emerged first from clinical research as a standard of care for advanced disease. Upon presenting key achievements in treatment outcomes with sorafenib, the author describes a plethora of failed phase III trials that tested many agents in first-line setting by using sorafenib as a control or in second-line treatment against placebo. 

In terms of systemic treatment, the author emphasizes that current options in first-line treatment are sorafenib and lenvatinib, while the second-line (post-sorafenib) treatment options are regorafenib in sorafenib tolerant patients, cabozantinib and ramucirumab in patients with AFP>400. Nivolumab and pembrolizumab have a high response and encouraging survival rate but results of randomised clinical trials are awaited. Combinations have promising response rates and randomised clinical trials are ongoing.

In terms of TACE and systemic therapy combinations, the author underlines that all four large phase III trials combining TACE with anti-angiogenic tyrosine kinase inhibitors are negative. Therefore, a different combination strategy needs to be considered. He highlights ongoing trials with TACE and immunotherapy. 

In terms of SIRT, three randomised trials failed to meet the primary endpoint of superiority to sorafenib alone. Although tolerability and response are encouraging, the questions remain around the need for dosimetry to improve outcomes, the optimal patient group and the high rate of patients in intention-to-treat group that failed to receive allocated SIRT therapy. Therefore, the place of SIRT in the treatment of hepatocellular carcinoma remains to be determined.  

As future challenges, the author underlines the determination of optimal sequence or combination therapy, the determination of predictive biomarkers of response to immune checkpoint inhibitors, the development of effective adjuvant systemic therapy for locoregional and surgical interventions, defining the role of SIRT, as well as revising endpoints to meet the demands of recent therapeutic advances.

This E-Learning module was published in 2019 and expired in 2021.

Last update: 18 Sep 2019

The author has reported to have contributed to advisory boards and conducted trials sponsored by the following: Eisai (lenvatinib), MSD (pembrolizumab), BMS (Nivolumab), Bayer (sorafenib and regorafenib), Ipsen (cabozantinib), BTG (DC Beads), Beigene (Tizlelizumab).

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