Internal Medicine, Gastroenterology And Hepatology, Fondazione Policlinico Universitario Agostino Gemelli Irccs, Università Cattolica Del Sacro Cuore, ROMA, ITALY.
Expert Opin Pharmacother. 2021 Jul;22(10):1343-1354. doi: 10.1080/14656566.2021.1892074. Epub 2021 Mar 3.
Although hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, there are limited therapeutic options for the advanced stages. Sorafenib was the first tyrosine-kinase inhibitor (TKI) approved for unresectable HCC and remained the only effective choice for a decade. The horizon of systemic treatments drastically expanded in the latest years, opening new interesting possibilities.
In this manuscript, the authors have analysed the recent advances in pharmacotherapy for HCC, discussing their mechanisms of action, the clinical efficacy and the safety profile of currently available first, second-and third-line treatments. The authors have also analysed the role of immune system modulators, in particular immune checkpoints inhibitors (ICIs), based on the limited data published so far.
The emergence of new targeted therapies, such as lenvatinib, have changed the landscape of HCC therapy. Tumor extension, differences in objective response rates and adverse events profiles should be considered to tailor the choice of the first-line agent. Sorafenib remains the most studied drug, with much real-world data available. The efficacy of second line therapies has only been proven in non-responder or sorafenib-intolerant patients. Unfortunately, studies directly comparing the second-line agents regorafenib, ramucirumab and cabozantinib are still lacking.
尽管肝细胞癌（HCC）是最常见的原发性肝癌，但晚期肝癌的治疗选择有限。索拉非尼是第一种被批准用于不可切除 HCC 的酪氨酸激酶抑制剂（TKI），并且在十年内仍然是唯一有效的选择。近年来，系统治疗的前景有了巨大的扩展，为患者提供了新的治疗选择。
在本文中，作者分析了 HCC 药物治疗的最新进展，讨论了目前可用的一线、二线和三线治疗药物的作用机制、临床疗效和安全性概况。作者还根据迄今为止发表的有限数据，分析了免疫系统调节剂（特别是免疫检查点抑制剂）的作用。
新型靶向治疗药物的出现，如仑伐替尼，改变了 HCC 治疗的格局。肿瘤的扩展、客观缓解率和不良反应谱的差异应考虑在内，以选择一线治疗药物。索拉非尼仍然是研究最多的药物，有大量的真实世界数据。二线治疗的疗效仅在无应答或不耐受索拉非尼的患者中得到证实。不幸的是，目前仍然缺乏对二线药物regorafenib、ramucirumab 和 cabozantinib 进行直接比较的研究。
