Immune therapies in intermediate-advanced unresectable hepatocellular carcinoma: Changing the therapeutic landscape

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. A substantial proportion of patients are diagnosed with advanced or intermediate-advanced stage disease at presentation and are often ineligible for curative surgery. The mainstay of treatment of this unique intermediate-advanced stage patients who have a liver-limited disease but unresectable due to large tumor burden, number of lesions or technical difficulties, have traditionally been locoregional therapies. However, the response has not been satisfactory in the majority of patients. With the advent of immune therapies and the remarkable progress it has made over the past decade, the management of intermediate-advanced HCC has undergone a paradigm change. Till 2020, sorafenib, a multi-targeted inhibitor of vascular endothelial growth factor, platelet-derived growth factor and rapidly accelerated fibrosarcoma was the one approved immune therapy. However, since 2021, nine more drugs have been approved, based on studies showing improved survival in advanced-stage HCC patients. However, the challenge clinicians face now is to determine the best choice/combination of available drugs to achieve long-term success and survival while maintaining preserved liver function. In light of emerging literature concerning immune therapies, including the relevant randomized controlled trial by Han et al, this editorial aims to review the currently available treatment strategies for the intermediate-advanced stage HCC.