ANN-LII CHENGCHIUN HSUChan S.L.Choo S.-P.Kudo M.2021-08-312021-08-3120200168-8278https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076577762&doi=10.1016%2fj.jhep.2019.09.025&partnerID=40&md5=1c14d8c327bbaa16801cc6f20df44af1https://scholars.lib.ntu.edu.tw/handle/123456789/580034Immune 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. ? 2019 European Association for the Study of the Liver[SDGs]SDG3angiogenesis inhibitor; checkpoint kinase inhibitor; immunomodulating agent; programmed death 1 ligand 1; programmed death 1 receptor; tumor marker; vasculotropin; vasculotropin inhibitor; vasculotropin receptor; angiogenesis inhibitor; CD274 protein, human; CTLA4 protein, human; cytotoxic T lymphocyte antigen 4; immunological antineoplastic agent; monoclonal antibody; PDCD1 protein, human; programmed death 1 ligand 1; programmed death 1 receptor; tumor marker; advanced cancer; antineoplastic activity; cancer combination chemotherapy; cancer immunotherapy; cancer survival; human; immunopathology; liver cell carcinoma; monotherapy; phase 3 clinical trial (topic); priority journal; randomized controlled trial (topic); Review; systematic review; treatment response; blood; drug therapy; immunology; immunotherapy; liver cell carcinoma; liver tumor; multimodality cancer therapy; pharmacology; procedures; T lymphocyte; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Hepatocellular; Combined Modality Therapy; CTLA-4 Antigen; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Liver Neoplasms; Programmed Cell Death 1 Receptor; Progression-Free Survival; T-Lymphocytesreview10.1016/j.jhep.2019.09.025319544942-s2.0-85076577762