Advanced hepatocellular carcinoma, known for its dismal prognosis, is a disease that is challenging to treat. For almost a decade, sorafenib was the only available treatment. However, the last two to three years have witnessed a true revolution in systemic treatment options for this lethal disease. Several targeted therapies with mostly anti-angiogenic properties have been developed and immunotherapy has made its entrance into the field. Furthermore, a growing understanding of the molecular pathways involved in hepatocarcinogenesis and new insights in tumour-immunobiology have led to the development of rational combination therapies, showing very promising results in a myriad of ongoing clinical trials. Here we review the latest developments and discuss the main consequences for clinical practice.

(BELG J MED ONCOL 2020;14(7):339-46)