Role of immune checkpoint inhibitor combinations in resectable and unresectable, embolization-eligible hepatocellular carcinoma

Immune checkpoint inhibitor (ICI) combination regimens have recently become the new standard of care for advanced hepatocellular carcinoma (HCC). Large, phase III registrational trials of ICI-containing regimens in resectable and embolization-eligible settings are now reading out. This review summarizes and critically appraises efficacy and safety data from these studies with consideration of the optimal use of ICIs in conjunction with antiangiogenic agents including important issues in management of HCC across the continuum of care such as those related to patient selection, treatment sequencing, and liver preservation. IMbrave050 assessed atezolizumab plus bevacizumab in resected HCC and EMERALD-1 and LEAP-012 evaluated addition of durvalumab-bevacizumab and pembrolizumab-lenvatinib to transarterial chemoembolization in unresectable, embolization-eligible HCC. Both EMERALD-1 and LEAP-012 met the primary endpoint of progression-free survival. While IMbrave050 initially met its primary endpoint of recurrence-free survival, the adjuvant atezolizumab-bevacizumab benefit was not maintained in an updated analysis. Survival benefits remain unclear for all phase III trials. Safety outcomes can be generally described as predictable based on experience with the respective experimental regimens in the advanced setting. Treatment selection in embolization-eligible settings should consider risks and benefits with special consideration of liver preservation. Additional research is required to optimize ICI combination use in the perioperative and peri-embolization settings.