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Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma

2020; Elsevier BV; Volume: 72; Issue: 2 Linguagem: Inglês

10.1016/j.jhep.2019.09.025

1600-0641

Ann‐Lii Cheng, Chiun Hsu, Stephen L. Chan, Su Pin Choo, Masatoshi Kudo,

Renal cell carcinoma treatment

Immune checkpoint inhibitor (ICI) therapy targeting anti-programmed cell death-1 (anti-PD-1) or its ligand (anti-PD-L1) is the backbone of numerous combination regimens aimed at improving the objective response and survival of patients with hepatocellular carcinoma (HCC). Clinical trials of immuno-oncology regimens in other cancer types have shed light on issues of study design, including how to choose candidate regimens based on early-phase trial results, statistical considerations in trials with multiple primary endpoints, and the importance of predictive biomarkers. In this review, the updated data from early-phase trials of combination immunotherapy for HCC are summarised. Since the most extensively tested combination regimens for advanced HCC comprise anti-PD-1/anti-PD-L1 agents plus antiangiogenic agents, the relative benefit and antitumor mechanism of antiangiogenic multikinase inhibitors versus specific VEGF/VEGFR inhibitors are discussed. Other critical issues in the development of combination immunotherapy, including optimal management of immune-related adverse events and the value of ICI therapy in combination with locoregional treatment for HCC, are also explored.