• Vito Longo, Oronzo Brunetti, Antonio Gnoni, Antonella Licchetta, Sabina Delcuratolo, Riccardo Memeo, Antonio Giovanni Solimando, and Antonella Argentiero.
• Medical Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, 70124 Bari, Italy. vito.longo79@tiscali.it.
• Medicina (Kaunas). 2019 Oct 17; 55 (10).

AbstractHepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standardcare for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results inan alternative first-line treatment for the Chineseclinical oncology guidelines. Moreover,nivolumab and pembrolizumab,two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approvedfor subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessmentof new ICIs-based combinatory approaches.

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