How have treatments for hepatocellular carcinoma improved?

Researchers at the Hospital Clínic-IDIBAPS and the University of Barcelona have published a review article in the journal Nature Cancer in which they describe the molecular alterations observed in the evolution of hepatocellular carcinoma, the most common type of liver cancer, and propose a sequencing strategy for systemic treatment, incorporating all the therapies approved to date.

The article was coordinated by Dr. Josep M. Llovet, Professor at the Faculty of Medicine and Health Sciences at UB, ICREA Research Professor at IDIBAPS where he leads the Translational Research in Hepatic Oncology group, and Director of the Liver Cancer Program at the Icahn School of Medicine at Mount Sinai in New York. Dr. Roser Pinyol, from the same IDIBAPS research group and lecturer at the Faculty of Medicine and Health Sciences at UB, also participated.

Hepatocellular carcinoma (HCC) accounts for over 90% of all cases of liver cancer and is the second leading cause of death due to cancer, with its incidence growing worldwide. The life expectancy of patients with this cancer has improved with the implementation of immunotherapy and targeted therapies.

Although the main molecular characteristics of HCC have been identified, and the immune classes -which indicate whether a tumour will respond to immunotherapy or not- have been defined, only 25% of tumours have a target for which treatment is available.

Advanced hepatocellular carcinoma is resistant to chemotherapy and radiotherapy, which limits the therapeutic options. In 2007, the approval of sorafenib, the first systemic treatment for HCC, radically changed the outlook for patients. Since then, different first- and second-line systemic treatments have been approved.

A new era in the treatment of hepatocellular carcinoma

In 2020, a new stage in the treatment of the disease began, based on the use of immunotherapy combinations. This is due to the superiority of the combination of atezolizumab (a PD-L1 inhibitor that boosts the immune system’s ability to attack cancer cells) and bevacizumab (an inhibitor that slows down the formation of new blood vessels) over sorafenib, in terms of improved progression-free and overall survival.

In this review, the researchers provide an integrated description of the molecular mechanisms that define the origin and evolution of HCC (Figure 1), as well as the oncogenic drivers and the molecular and immune classes. The latest advances in the approval of other molecular and immune systemic therapies are also assessed, and a new therapeutic scheme is provided that integrates all the currently available drugs and their sequencing.

On the other hand, “we assess how this knowledge can be transferred to precision oncology providing a perspective on the role of systemic therapies in HCC in the management of the disease and the transition from local-regional to systemic treatments”. “Finally, we are proposing a new sequencing scheme for systemic treatment, which integrates all the currently approved drugs and the hierarchy of use", says Dr. Llovet.

The article also compiles existing evidence on the new molecular and immune therapies in the early stages of clinical trials to help in clinical decision-making, as well as information about new clinical trials and biomarkers and the design of trials for future research.

Article reference:

Llovet JM, Pinyol R, Kelley RK, El-Khoueiry A, Reeves HL, Wang XW, Gores GJ, Villanueva A. Molecular pathogenesis and systemic therapies for hepatocellular carcinoma. Nat Cancer 2022 ;3:386-401. doi: 10.1038/s43018-022-00357-2. Epub 2022 Apr 28.