Since the approval of sorafenib for patients with advanced hepatocellular carcinoma (HCC) in 2007, many drugs have failed in the first and second-line setting. Fortunately, during the recent 2 years, between 2017 and 2018, four drugs (regorafenib, lenvatinib, cabozantinib, and ramucirumab) were found to be effective and tolerable for patients with HCC as the first-or second-line therapy. Regorafenib, a multi-kinase inhibitor, has a similar structure to sorafenib, and was shown to improve the

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... vival of patients who progressed after sorafenib treatment compared to the placebo control. According to the phase III trial of regorafenib, it became the first approved systemic therapy for patients with progression after sorafenib. Lenvatinib is also a tyrosine kinase inhibitor (TKI), and in a phase III trial comparing sorafenib and lenvatinib, the primary end-point of non-inferior survival was met. Based on the trial results, lenvatinb has become another systemic therapy for treatment-naïve patients with advanced HCC. Cabozantinib is a dual inhibitor of Mesenchymal-Epithelial Transition factor/Vascular Endothelial Growth Factor Receptor2, and was shown to prolong the overall survival in patients who progressed after sorafenib compared to the placebo. Ramucirumab is a monoclonal antibody to inhibit a single target of VEGFR2. First, this drug failed to improve the survival of patients who progressed after sorafenib failure. On the other hand, it was effective in patients with baseline AFP ≥400 ng/mL. In a subsequent clinical trial that enrolled only patients with AFP ≥400 ng/mL, ramucirumab was also found to improve the overall survival compared to placebo. Thus, ramucirumab became the first biomarker-driven systemic treatment. Another category of drugs that are attracting considerable interest are immune checkpoint inhibitors, such as anti-programmed cell death protein (PD) 1 or anti-PD-ligand 1. This review provides a synopsis of new systemic therapies, including TKI, monoclonal antibody, and immune-oncology drugs. ( Korean J Gastroenterol 2019;73:10-15) 서 론 간세포암종은 원발성 간암의 90% 이상을 차지하는 고형암 으로 재발이 흔하고, 동반될 수 있는 간경변증과 같은 만성 간질환으로 인하여 전체적으로 생존율이 1년을 넘지 못하는, 예후가 불량한 암종으로 잘 알려져 있다. 1 특히, 고위험군에 대한 감시 검사가 시행되고 있음에도 불구하고, 근치적 치료가 가능한 초기 병기를 넘어선 진행성 간세포암종으로 진단되는 환자들이 여전히 많다. 일반적으로 진행성 간세포암종은 Barcelona Clinic Liver Cancer 병기 분류에 따라 문맥 침윤 이 있거나 간외 전이가 동반한 경우로 정의된다. 2 현재 진행성 간세포암종의 표준 치료는 전신 치료 또는 표적 치료로 불리는 tyrosine kinase inhibitor (TKI)인 sorafenib이다. 이 약물이 임상에 도입된