肝癌分子靶向药物及免疫抑制剂治疗的研究现状及进展

doi:10.3877/cma.j.issn.2095-5782.2019.03.015

肝癌是全球癌症发病率第6位，死亡率第3位的恶性肿瘤。肝癌发病隐匿且发展迅速，多数患者发现时病情就已经进展到中晚期，丧失了手术根治的机会。索拉非尼作为抗血管生成的分子靶向药物开启了肝癌分子靶向治疗的先河，在随后的近十年内，针对肝癌的靶向药物不断涌现，瑞戈非尼、乐伐替尼、卡博替尼、雷莫芦单抗以及一些免疫抑制剂在Ⅲ期临床试验方面取得了不错的成绩。本文就新出现的抗血管分子靶向药物及免疫抑制剂治疗肝癌的现状、挑战以及未来的发展方向进行综述。

关键词: 肝癌, 系统治疗, 分子靶向治疗, 免疫治疗

Hepatic carcinoma (HCC) is the sixth most common malignant tumor in the world and the third leading cause of death. Due to the hidden nature of onset of HCC, most patients are already at the intermediate or advanced stage at the time of diagnosis and are not candidates for curative surgical treatment. Sorafenib, as a molecular targeted drug against angiogenesis, has opened the door of molecular targeted therapy for HCC since 2007, systemic treatment has become one of the hotspots in the treatment of HCC. In the following decade, targeted drugs for HCC developed, such as regorafenib, levovirinib, cabozantinib, remollozumab and some immune checkpoint inhibitors, and they have achieved good results in phase III clinical trials. This review describes the current status of anti-vascular molecular targeted therapy and immunosuppressive agents in the treatment of HCC, the challenges to be solved and the possible future development.

Key words: Hepatocellular carcinoma, Systemic therapy, Molecular targeted therapy, Immunotherapy

表1 晚期肝癌的三期临床试验

目标人群	实验设计	试验名称	实验结果
预防复发	索拉非尼对比安慰剂	STORM	阴性
增强TACE疗效	TACE±索拉非尼	Post-TACE	阴性
增强TACE疗效	TACE±索拉非尼	SPACE	阴性
增强TACE疗效	TACE±索拉非尼	TACE 2	阴性
增强TACE疗效	TACE±索拉非尼	TACTICS	阳性
一线治疗	索拉非尼对比乐伐替尼	REFLECT	阳性
二线治疗	瑞戈非尼对比安慰剂	RESORCE	阳性
二线治疗	卡博替尼对比安慰剂	CELESTIAL	阳性
二线治疗	雷莫芦单抗对比安慰剂	REACH-2	阳性
一线治疗	索拉非尼对比纳武单抗	CheckMate-459	正在进行
二线治疗	派姆单抗对比安慰剂	KEYNOTE-240	阴性

表1 晚期肝癌的三期临床试验

目标人群	实验设计	试验名称	实验结果
预防复发	索拉非尼对比安慰剂	STORM	阴性
增强TACE疗效	TACE±索拉非尼	Post-TACE	阴性
增强TACE疗效	TACE±索拉非尼	SPACE	阴性
增强TACE疗效	TACE±索拉非尼	TACE 2	阴性
增强TACE疗效	TACE±索拉非尼	TACTICS	阳性
一线治疗	索拉非尼对比乐伐替尼	REFLECT	阳性
二线治疗	瑞戈非尼对比安慰剂	RESORCE	阳性
二线治疗	卡博替尼对比安慰剂	CELESTIAL	阳性
二线治疗	雷莫芦单抗对比安慰剂	REACH-2	阳性
一线治疗	索拉非尼对比纳武单抗	CheckMate-459	正在进行
二线治疗	派姆单抗对比安慰剂	KEYNOTE-240	阴性

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Current situation and research advances of molecular targeted drugs and immunosuppressive therapy for hepatocellular carcinoma

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Current situation and research advances of molecular targeted drugs and immunosuppressive therapy for hepatocellular carcinoma