经肝动脉化疗栓塞术联合靶向/免疫治疗在中晚期肝细胞癌中的应用进展

赵晓辉; 姚全军; 黎海亮; 胡鸿涛

doi:10.3969/j.issn.1001-5256.2022.12.033

经肝动脉化疗栓塞术联合靶向/免疫治疗在中晚期肝细胞癌中的应用进展

DOI: 10.3969/j.issn.1001-5256.2022.12.033

郑州大学附属肿瘤医院(河南省肿瘤医院) 微创介入科，郑州 450008

基金项目:

河南省自然科学基金面上项目 (212300410403);

2022年度河南省人力资源和社会保障厅留学人员科研择优资助项目 ;

河南省医学教育研究项目 (Wjlx2021334)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：黎海亮、胡鸿涛对研究的思路或设计有关键贡献；赵晓辉、姚全军参与起草或修改文章关键内容。

详细信息

通信作者:
胡鸿涛，huhongtaogy@163.com

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出版历程
- 收稿日期: 2022-04-11
- 录用日期: 2022-06-15
- 出版日期: 2022-12-20

Advances in application of transarterial chemoembolization combined with targeted therapy/immunotherapy in advanced hepatocellular carcinoma

Department of Minimally Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University & Cancer Hospital of Henan Province, Zhengzhou 450008, China

Research funding:

Henan Provincial Natural Science Foundation General Project (212300410403);

2022 Henan Provincial Department of Human Resources and Social Security Research Scholarship for Overseas Students ;

2022 Henan Provincial Department of Human Resources and Social Security Research Scholarship for Overseas Students; Henan Provincial Medical Education Research Project (Wjlx2021334)

More Information

Corresponding author: HU Hongtao, huhongtaogy@163.com (ORCID: 0000-0002-5432-4014)

摘要

摘要: 我国肝细胞癌患者发现时多为中晚期，其治疗方法主要包括经肝动脉化疗栓塞术(TACE)和系统治疗。本文介绍了从索拉非尼、仑伐替尼为代表的靶向药物，再到免疫治疗的异军突起——阿替利珠单抗联合贝伐珠单抗获批一线治疗方案，同时TACE联合靶向和/或免疫治疗的研究也在进行中，取得了较好的疗效，这些都为中晚期肝癌患者带来了更好的生存预后。但是，想要真正改变中晚期肝癌预后的问题，仍需要在此基础上进行更多的探索与研究。
- 癌，肝细胞 /
- 靶向治疗 /
- 免疫疗法 /
- 化学栓塞，治疗性
Abstract: Most of the patients with hepatocellular carcinoma (HCC) in China are in the advanced stage at the time of diagnosis, and the treatment methods for HCC mainly include transarterial chemoembolization and systemic therapy. This article introduces the targeted drugs represented by sorafenib and lenvatinib, and the emergence of immunotherapy. Atezolizumab combined with bevacizumab has been approved as the first-line therapy for HCC, and meanwhile, studies on TACE combined with targeted therapy and/or immunotherapy have achieved a satisfactory treatment outcome, which brings better survival and prognosis for patients with advanced HCC. However, more studies are needed to solve the issues related to the prognosis of advanced HCC.
- Carcinoma, Hepatocellular /
- Targeted Therapy /
- Immunotherapy /
- Chemoembolization, Therapeutic

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参考文献(39)

[1]	CHENG AL, KANG YK, CHEN Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase Ⅲ randomised, double-blind, placebo-controlled trial[J]. Lancet Oncol, 2009, 10(1): 25-34. DOI: 10.1016/S1470-2045(08)70285-7.
[2]	LLOVET JM, RICCI S, MAZZAFERRO V, et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med, 2008, 359(4): 378-390. DOI: 10.1056/NEJMoa0708857.
[3]	QIN S, BAI Y, LIM HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia[J]. J Clin Oncol, 2013, 31(28): 3501-3508. DOI: 10.1200/JCO.2012.44.5643.
[4]	KUDO M, FINN RS, QIN S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391(10126): 1163-1173. DOI: 10.1016/S0140-6736(18)30207-1.
[5]	QIN S, BI F, GU S, et al. Donafenib versus sorafenib in first-line treatment of unresectable or metastatic hepatocellular carcinoma: a randomized, open-label, parallel-controlled phase Ⅱ-Ⅲ trial[J]. J Clin Oncol, 2021, 39(27): 3002-3011. DOI: 10.1200/JCO.21.00163.
[6]	EL-KHOUEIRY AB, SANGRO B, YAU T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial[J]. Lancet, 2017, 389(10088): 2492-2502. DOI: 10.1016/S0140-6736(17)31046-2.
[7]	YAU T, PARK JW, FINN RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial[J]. Lancet Oncol, 2022, 23(1): 77-90. DOI: 10.1016/S1470-2045(21)00604-5.
[8]	FINN RS, IKEDA M, ZHU AX, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2020, 38(26): 2960-2970. DOI: 10.1200/JCO.20.00808.
[9]	FINN RS, QIN S, IKEDA M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382(20): 1894-1905. DOI: 10.1056/NEJMoa1915745.
[10]	DUCREUX M, ZHU A X, CHENG A L, et al. IMbrave150: Exploratory analysis to examine the association between treatment response and overall survival (OS) in patients (pts) with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab (atezo)+ bevacizumab (bev) versus sorafenib (sor)[C]. 2021 ASCO Annual Meeting I. Chicago, 2021.
[11]	REN Z, XU J, BAI Y, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study[J]. Lancet Oncol, 2021, 22(7): 977-990. DOI: 10.1016/S1470-2045(21)00252-7.
[12]	XU J, SHEN J, GU S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase Ⅱ trial[J]. Clin Cancer Res, 2021, 27(4): 1003-1011. DOI: 10.1158/1078-0432.CCR-20-2571.
[13]	GALLE PR, KIM RD, SUNG MW, et al. 990P Updated results of a phase Ib study of regorafenib (REG) plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC)[C]. 2020 European Society for Medical Oncology. Paris, 2020.
[14]	ZENG Z, ZHANG L, WU T, et al. A retrospective study on the efficacy and safety of sorafenib or lenvatinib combined with sintilimab in patients with advanced hepatocellular carcinoma[C]. 2021 ASCO Annual Meeting I. Chicago, 2021.
[15]	EL-KHOUEIRY AB, KIM RD, HARRIS WP, et al. Updated results of a phase 1b study of regorafenib (REG) 80 mg/day or 120 mg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC)[C]. 2021 ASCO Annual Meeting I. Chicago, 2021.
[16]	CERRITO L, ANNICCHIARICO BE, IEZZI R, et al. Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers[J]. World J Gastroenterol, 2019, 25(31): 4360-4382. DOI: 10.3748/wjg.v25.i31.4360.
[17]	XUE TC, XIE XY, ZHANG L, et al. Transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a meta-analysis[J]. BMC Gastroenterol, 2013, 13: 60. DOI: 10.1186/1471-230X-13-60.
[18]	PECK-RADOSAVLJEVIC M, KUDO M, RAOUL JL, et al. Outcomes of patients (pts) with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE): Global OPTIMIS final analysis[C]. 2018 ASCO Annual Meeting I. Chicago, 2018.
[19]	GUO J, WANG S, HAN Y, et al. Effects of transarterial chemoembolization on the immunological function of patients with hepatocellular carcinoma[J]. Oncol Lett, 2021, 22(1): 554. DOI: 10.3892/ol.2021.12815.
[20]	PETRILLO M, PATELLA F, PESAPANE F, et al. Hypoxia and tumor angiogenesis in the era of hepatocellular carcinoma transarterial loco-regional treatments[J]. Future Oncol, 2018, 14(28): 2957-2967. DOI: 10.2217/fon-2017-0739.
[21]	LIU K, MIN XL, PENG J, et al. The changes of HIF-1α and VEGF expression after TACE in patients with hepatocellular carcinoma[J]. J Clin Med Res, 2016, 8(4): 297-302. DOI: 10.14740/jocmr2496w.
[22]	UNRUH A, RESSEL A, MOHAMED HG, et al. The hypoxia-inducible factor-1 alpha is a negative factor for tumor therapy[J]. Oncogene, 2003, 22(21): 3213-3220. DOI: 10.1038/sj.onc.1206385.
[23]	MEYER T, FOX R, MA YT, et al. Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial[J]. Lancet Gastroenterol Hepatol, 2017, 2(8): 565-575. DOI: 10.1016/S2468-1253(17)30156-5.
[24]	LENCIONI R, LLOVET JM, HAN G, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial[J]. J Hepatol, 2016, 64(5): 1090-1098. DOI: 10.1016/j.jhep.2016.01.012.
[25]	CHEN YR, YAN D, YANG JD, et al. Effect of hepatic artery chemoembolization combined with sorafenib in the treatment of primary liver cancer and its influence on patients' immune function[J]. Clin J Med Offic, 2021, 49(3): 290-291. DOI: 10.16680/j.1671-3826.2021.03.16. 程瑜蓉, 严冬, 杨建东, 等. 肝动脉栓塞化疗联合索拉非尼在原发性肝癌治疗中应用效果及对患者免疫功能影响[J]. 临床军医杂志, 2021, 49(3): 290-291. DOI: 10.16680/j.1671-3826.2021.03.16.
[26]	KUDO M, UESHIMA K, IKEDA M, et al. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial[J]. Gut, 2020, 69(8): 1492-1501. DOI: 10.1136/gutjnl-2019-318934.
[27]	KUDO M, UESHIMA K, IKEDA M, et al. TACTICS: Final overall survival (OS) data from a randomized, open label, multicenter, phase Ⅱ trial of transcatheter arterial chemoembolization (TACE) therapy in combination with sorafenib as compared with TACE alone in patients (pts) with hepatocellular carcinoma (HCC)[C]. 2021 Gastrointestinal Cancers Symposium. Chicago, 2021.
[28]	LI W, KONG S, SU J, et al. Efficacy of transcatheter arterial chemoembolization combined with sorafenib in inhibiting tumor angiogenesis in a rabbit VX2 liver cancer model[J]. J Interv Med, 2020, 3(1): 27-33. DOI: 10.1016/j.jimed.2020.01.003.
[29]	LU W, JIN XL, YANG C, et al. Comparison of efficacy between TACE combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma: A single-center randomized controlled trial[J]. Cancer Biol Ther, 2017, 18(6): 433-438. DOI: 10.1080/15384047.2017.1323589.
[30]	DING X, SUN W, LI W, et al. Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A prospective randomized study[J]. Cancer, 2021, 127(20): 3782-3793. DOI: 10.1002/cncr.33677.
[31]	GRETEN TF, MAUDA-HAVAKUK M, HEINRICH B, et al. Combined locoregional-immunotherapy for liver cancer[J]. J Hepatol, 2019, 70(5): 999-1007. DOI: 10.1016/j.jhep.2019.01.027.
[32]	PARK H, JUNG JH, JUNG MK, et al. Effects of transarterial chemoembolization on regulatory T cell and its subpopulations in patients with hepatocellular carcinoma[J]. Hepatol Int, 2020, 14(2): 249-258. DOI: 10.1007/s12072-020-10014-4.
[33]	MONTASSER A, BEAUFRÀRE A, CAUCHY F, et al. Transarterial chemoembolisation enhances programmed death-1 and programmed death-ligand 1 expression in hepatocellular carcinoma[J]. Histopathology, 2021, 79(1): 36-46. DOI: 10.1111/his.14317.
[34]	SHIGETA K, DATTA M, HATO T, et al. Dual programmed death receptor-1 and vascular endothelial growth factor receptor-2 blockade promotes vascular normalization and enhances antitumor immune responses in hepatocellular carcinoma[J]. Hepatology, 2020, 71(4): 1247-1261. DOI: 10.1002/hep.30889.
[35]	ZHANG N, LIU XL, XU ZQ, et al. Research progress in relationship between tumor anti-angiogenesis and immunotherapy[J]. J Jilin Univ(Med Edit), 2021, 47(4): 1056-1063. DOI: 10.13481/j.1671-587X.20210434. 张娜, 刘相良, 徐志强, 等. 肿瘤抗血管生成及其与免疫治疗关系的研究进展[J]. 吉林大学学报(医学版), 2021, 47(4): 1056-1063. DOI: 10.13481/j.1671-587X.20210434.
[36]	YANG F, XU GL, HUANG JT, et al. Transarterial chemoembolization combined with immune checkpoint inhibitors and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: efficacy and systemic immune response[J]. Front Immunol, 2022, 13: 847601. DOI: 10.3389/fimmu.2022.847601.
[37]	CAI M, HUANG W, HUANG J, et al. Transarterial chemoembolization combined with lenvatinib plus PD-1 inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study[J]. Front Immunol, 2022, 13: 848387. DOI: 10.3389/fimmu.2022.848387.
[38]	LIU J, LI Z, ZHANG W, et al. Comprehensive treatment of trans-arterial chemoembolization plus lenvatinib followed by camrelizumab for advanced hepatocellular carcinoma patients[J]. Front Pharmacol, 2021, 12: 709060. DOI: 10.3389/fphar.2021.709060.
[39]	JU S, ZHOU C, YANG C, et al. Apatinib plus camrelizumab with/without chemoembolization for hepatocellular carcinoma: a real-world experience of a single center[J]. Front Oncol, 2021, 11: 835889. DOI: 10.3389/fonc.2021.835889.