Dong Y.TSUNG-HAO LIUYau T.CHIUN HSU2021-03-192021-03-1920201936-0533https://www.scopus.com/inward/record.uri?eid=2-s2.0-85089032113&doi=10.1007%2fs12072-020-10073-7&partnerID=40&md5=1190dc5d88e319ec13d28bda5f91337ahttps://scholars.lib.ntu.edu.tw/handle/123456789/553847Systemic therapy for hepatocellular carcinoma (HCC) used to be limited to patients with advanced diseases and multi-kinase inhibitors targeting tumor angiogenesis the major approach of developing new treatment options. In the past 3?years, new data from trials of both molecular targeted therapy and immune checkpoint inhibitors (ICI) provided many new options of first- and second-line treatment for advanced HCC. Most notably, combination of ICI targeting the program cell death-1 (PD-1) pathway with other novel agents or conventional anti-cancer therapy may further improve treatment efficacy in different clinical settings. In this?paper updated data of clinical trials of systemic therapy in the first- and second-line settings for advanced HCC were reviewed and the following issues were?discussed: (1) lessons of trial design learned from positive and negative trials; (2) the balance between efficacy and safety in clinical practice; and (3) impact on future multi-disciplinary management of HCC. ? 2020, Asian Pacific Association for the Study of the Liver.[SDGs]SDG3atezolizumab; bevacizumab; cabozantinib; cytotoxic T lymphocyte antigen 4; durvalumab; ipilimumab; lenvatinib; nivolumab; pembrolizumab; programmed death 1 receptor; ramucirumab; regorafenib; sorafenib; ticilimumab; abdominal pain; alopecia; anorexia; antiangiogenic activity; antineoplastic activity; asthenia; clinical practice; diarrhea; drug efficacy; drug safety; dysphonia; fatigue; hand foot syndrome; human; hypertension; liver cell carcinoma; molecularly targeted therapy; multidisciplinary team; nausea; nonhuman; overall survival; patient selection; priority journal; proteinuria; pruritus; randomized controlled trial (topic); rash; Review; study design; systemic therapy; vomiting; liver cell carcinoma; liver tumor; pathology; patient care; pharmacology; procedures; treatment outcome; Carcinoma, Hepatocellular; Humans; Immune Checkpoint Inhibitors; Liver Neoplasms; Molecular Targeted Therapy; Patient Care Management; Randomized Controlled Trials as Topic; Treatment Outcomereview10.1007/s12072-020-10073-7326619492-s2.0-85089032113