Immune checkpoint inhibitors for hepatocellular carcinoma - A game changer in treatment landscape

Abstract

Rapidly expanding armamentarium of systemic therapy for advanced hepatocellular carcinoma (HCC) occurred in the recent few years. Multikinase inhibitors (MKI) or targeted therapy with antiangiogenic properties have been the focus of clinical studies in advanced HCC in the past decade. The remarkable efficacy of single agent immune checkpoint inhibitors (ICI), including nivolumab and pembrolizumab, in early phase studies led to accelerated approvals as second-line treatment for advanced HCC. The excellent toxicity profile of single agent ICI also lends support to be developed as combination therapy with other targeted therapies. The success of combining atezolizumab and bevacizumab over sorafenib as the first-line treatment in advanced HCC marked the newest paradigm shift in advanced HCC. The combination exhibited unprecedented objective response rate of 30% and a median survival of 19.2 months. Many other similar ICI-based combinations are expected to be approved in the foreseeable future. In this narrative review, the development of ICI alone and in combination in advanced HCC were described and the potential impact in all stages of HCC, safety issues of ICI-based combinations, and future perspectives were discussed.

Keywords: Hepatocellular carcinoma; Immune checkpoint inhibitor; Targeted therapy.