Systemic Therapy for Hepatocellular Carcinoma: Latest Advances.
Systemic Therapy for Hepatocellular Carcinoma: Latest Advances.
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DOI：
10.3390/cancers10110412
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发表时间：
2018-10-30
期刊：
影响因子：
5.2
通讯作者：
Kudo M
中科院分区：
文献类型：
--
作者：
Kudo M
自2007年引入分子靶向药物索拉非尼以来，肝细胞癌（HCC）的全身治疗发生了巨大变化。尽管索拉非尼扩大了肝外播散（EHS）和血管浸润的治疗选择，使晚期疾病患者的长期生存在一定程度上得以实现，但由于其反应率低、毒性大等缺点，新的分子靶向药物正在被开发作为索拉非尼的替代品。从2007年到2016年的10年间，开发的许多药物中的每一种都是失败的。然而，在2017年至2018年的两年期间，四种药物--瑞戈非尼、乐伐替尼、卡博替尼和雷莫芦单抗--连续成功通过临床试验并投入临床使用。2018年，经导管动脉化疗栓塞术（TACE）联合索拉非尼联合治疗的疗效也首次得到证实。最近，免疫检查点抑制剂已被应用于HCC治疗，许多III期临床试验正在进行中，不仅是关于纳武单抗、派姆单抗和tislelizumab的单药治疗，而且还关于与检查点抑制剂的联合治疗，程序性死亡-1（PD-1）或PD-配体1（PD-L1）抗体加分子靶向药物（贝伐单抗）或细胞毒性T淋巴细胞相关抗原4（CTLA-4）抗体曲美木单抗。这些联合治疗显示出比PD-1/PD-L1单药治疗更高的缓解率，表明联合治疗在早期阶段具有协同作用;因此，迫切期待进一步的结果。
Systemic therapy for hepatocellular carcinoma (HCC) has changed drastically since the introduction of the molecular targeted agent sorafenib in 2007. Although sorafenib expanded the treatment options for extrahepatic spread (EHS) and vascular invasion, making long-term survival of patients with advanced disease achievable to a certain extent, new molecular-targeted agents are being developed as alternatives to sorafenib due to shortcomings such as its low response rate and high toxicity. Every single one of the many drugs developed during the 10-year period from 2007 to 2016 was a failure. However, during the two-year period from 2017 through 2018, four drugs—regorafenib, lenvatinib, cabozantinib, and ramucirumab—emerged successfully from clinical trials in quick succession and became available for clinical use. The efficacy of combination therapy with transcatheter arterial chemoembolization (TACE) plus sorafenib was also first demonstrated in 2018. Recently, immune checkpoint inhibitors have been applied to HCC treatment and many phase III clinical trials are ongoing, not only on monotherapy with nivolumab, pembrolizumab, and tislelizumab, but also on combination therapy with checkpoint inhibitors, programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) antibody plus a molecular targeted agent (bevacizumab) or the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, tremelimumab. These combination therapies have shown higher response rates than PD-1/PD-L1 monotherapy alone, suggesting a synergistic effect by combination therapy in early phases; therefore, further results are eagerly awaited.
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影响因子：
35.7
作者：
Kudo, Masatoshi;Moriguchi, Michihisa;Okusaka, Takuji
通讯作者：
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作者：
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影响因子：
51.1
作者：
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影响因子：
3
作者：
Chang, Yong S.;Adnane, Jalila;Wilhelm, Scott
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