Research advances in transcatheter arterial chemoembolization combined with targeted agents or anti-PD-1/PD-L1 monoclonal antibody in treatment of patients with unresectable hepatocellular carcinoma

Qiuju PENG; Tao DAI; Guibo XIE; Jinjun CHEN; Xiao CHENG; Yuan YAN

doi:10.3969/j.issn.1001-5256.2023.07.033

Volume 39 Issue 7

Jul. 2023

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Article Navigation > Journal of Clinical Hepatology > 2023 > 39(7): 1740-1746

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Research advances in transcatheter arterial chemoembolization combined with targeted agents or anti-PD-1/PD-L1 monoclonal antibody in treatment of patients with unresectable hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2023.07.033

a.
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
b.
Department of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Research funding:

National Natural Science Foundation of China (82070650);

National Science and Technology Major Project (2018ZX10723203);

National Science and Technology Major Project (2018ZX10302206)

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Corresponding author: YAN Yuan, 616756657@qq.com (ORCID: 0000-0002-1044-2457)
Received Date: 2022-10-31
Accepted Date: 2022-12-18
Published Date: 2023-07-20

Abstract

Abstract

Transcatheter arterial chemoembolization (TACE) is recommended by domestic and international guidelines for the treatment of patients with unresectable hepatocellular carcinoma (uHCC), and it is one of the most common treatment methods for patients with uHCC. The chemotherapy drugs commonly used in TACE for HCC include epirubicin, cisplatin, and fluorouracil, while it is still unclear which chemotherapy drug has a better clinical effect. This article summarizes the studies of different TACE regimens using different chemotherapy drugs in the treatment of patients with uHCC in the recent five years. TACE combined with sorafenib can significantly improve the survival of patients with advanced HCC and has been recommended for the treatment of such patients by Chinese Society of Clinical Oncology guidelines, and the efficacy of TACE combined with other tyrosine kinase inhibitors (TKI) has become a research hotspot. Studies have shown that compared with TACE combined with sorafenib in the treatment of patients with advanced HCC, TACE combined with lenvatinib can achieve a significantly longer progression-free survival time and a tendency of increase in median overall survival time. However, due to the variation of target receptors or downstream signals, resistance to molecular-targeted agents is still a challenging problem. TKI combined with immune checkpoint inhibitors may be a promising strategy for the treatment of patients with uHCC. Some studies suggest that triple therapy using TACE combined with TKIs and anti-PD-1/PD-L1 monoclonal antibody has better efficacy in improving the survival of patients with uHCC. This article reviews the studies of the efficacy and safety of TACE combined with targeted agents and TACE combined with anti-PD-1/PD-L1 monoclonal antibody in the treatment of patients with uHCC in the recent five years.
- Carcinoma, Hepatocellular,
- Chemoembolization, Therapeutic,
- Molecular Targeted Therapy,
- Immune Checkpoint Inhibitors,
- Drug Therapy, Combination

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References

[1]	SUNG H, FERLAY J, SIEGEL RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
[2]	BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.
[3]	Chinese Society of Clinical Oncology. Guidelines for diagnosis and treatment of primary liver cancer (2022 edition)[M]. Beijing: People's Medical Publishing House, 2022. 中国临床肿瘤学会. 原发性肝癌诊疗指南(2022年版)[M]. 北京: 人民卫生出版社, 2022.
[4]	NCCN. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^Ⓡ)[EB/OL]. Hepatobiliary Cancers. Version 1.2022. https://www.nccn.org/.
[5]	RAOUL JL, FORNER A, BOLONDI L, et al. Updated use of TACE for hepatocellular carcinoma treatment: How and when to use it based on clinical evidence[J]. Cancer Treat Rev, 2019, 72: 28-36. DOI: 10.1016/j.ctrv.2018.11.002.
[6]	LO CM, NGAN H, TSO WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma[J]. Hepatology, 2002, 35(5): 1164-1171. DOI: 10.1053/jhep.2002.33156.
[7]	LLOVET JM, REAL MI, MONTAÑA X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial[J]. Lancet, 2002, 359(9319): 1734-1739. DOI: 10.1016/S0140-6736(02)08649-X.
[8]	ARAMAKI O, TAKAYAMA T, MORIGUCHI M, et al. Arterial chemoembolisation with cisplatin versus epirubicin for hepatocellular carcinoma (ACE 500 study): A multicentre, randomised controlled phase 2/3 trial[J]. Eur J Cancer, 2021, 157: 373-382. DOI: 10.1016/j.ejca.2021.08.027.
[9]	IKEDA M, KUDO M, AIKATA H, et al. Transarterial chemoembolization with miriplatin vs. epirubicin for unresectable hepatocellular carcinoma: a phase Ⅲ randomized trial[J]. J Gastroenterol, 2018, 53(2): 281-290. DOI: 10.1007/s00535-017-1374-6.
[10]	Chinese College of Interventionalists, Chinese Medical Doctor Association. Chinese clinical practice guidelines for transarterial chemoembolization of hepatocellular carcinoma[J]. Chin J Intern Med, 2021, 60(7): 599-614. DOI: 10.3760/cma.j.cn112137-20210425-00991. 中国医师协会介入医师分会临床诊疗指南专委会. 中国肝细胞癌经动脉化疗栓塞(TACE)治疗临床实践指南(2021年版)[J]. 中华内科杂志, 2021, 60(7): 599-614. DOI: 10.3760/cma.j.cn112137-20210425-00991.
[11]	FU J, WANG Y, ZHANG J, et al. The safety and efficacy of transarterial chemoembolisation with bleomycin for hepatocellular carcinoma unresponsive to doxorubicin: a prospective single-centre study[J]. Clin Radiol, 2021, 76(11): 864. e7-864. e12. DOI: 10.1016/j.crad.2021.07.013.
[12]	WANG Y, FU JX, ZHANG JL, et al. Transarterial chemoembolization with bleomycin treatment for moderate-advenced hepatocellular carcinoma[J]. Nat Med J China, 2018, 98(39): 3166-3170. DOI: 10.3760/cma.j.issn.0376-2491.2018.39.008. 王燕, 付金鑫, 张金龙, 等. 博来霉素经肝动脉化疗栓塞治疗中晚期肝癌的临床观察[J]. 中华医学杂志, 2018, 98(39): 3166-3170. DOI: 10.3760/cma.j.issn.0376-2491.2018.39.008.
[13]	BESSAR AA, FARAG A, ABDEL MONEM SM, et al. Transarterial chemoembolisation in patients with hepatocellular carcinoma: low-dose doxorubicin reduces post-embolisation syndrome without affecting survival-prospective interventional study[J]. Eur Radiol Exp, 2021, 5(1): 10. DOI: 10.1186/s41747-021-00204-6.
[14]	ZHANG Z, WU Y, ZHENG T, et al. Efficacy of transarterial chemoembolization combined with molecular targeted agents for unresectable hepatocellular carcinoma: A network meta-analysis[J]. Cancers (Basel), 2022, 14(15). DOI: 10.3390/cancers14153710.
[15]	SCHICHO A, HELLERBRAND C, KRÜGER K, et al. Impact of different embolic agents for transarterial chemoembolization (TACE) procedures on systemic vascular endothelial growth factor (VEGF) levels[J]. J Clin Transl Hepatol, 2016, 4(4): 288-292. DOI: 10.14218/JCTH.2016.00058.
[16]	SERGIO A, CRISTOFORI C, CARDIN R, et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness[J]. Am J Gastroenterol, 2008, 103(4): 914-921. DOI: 10.1111/j.1572-0241.2007.01712.x.
[17]	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.
[18]	LEE TY, LIN CC, CHEN CY, et al. Combination of transcatheter arterial chemoembolization and interrupted dosing sorafenib improves patient survival in early-intermediate stage hepatocellular carcinoma: A post hoc analysis of the START trial[J]. Medicine (Baltimore), 2017, 96(37): e7655. DOI: 10.1097/MD.0000000000007655.
[19]	XU X, MENG Q. Drug effect analysis of sorafenib combined with transcatheter arterial chemoembolization in the treatment of advanced hepatocellular carcinoma[J]. Pak J Pharm Sci, 2018, 31(4(Special)): 1751-1755.
[20]	CAI R, SONG R, PANG P, et al. Transcatheter arterial chemoembolization plus sorafenib versus transcatheter arterial chemoembolization alone to treat advanced hepatocellular carcinoma: a meta-analysis[J]. BMC Cancer, 2017, 17(1): 714. DOI: 10.1186/s12885-017-3707-5.
[21]	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.
[22]	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.
[23]	ZHAO S, ZHANG T, DOU W, et al. A comparison of transcatheter arterial chemoembolization used with and without apatinib for intermediate- to advanced-stage hepatocellular carcinoma: a systematic review and meta-analysis[J]. Ann Transl Med, 2020, 8(8): 542. DOI: 10.21037/atm.2020.02.125.
[24]	CAO Y, SUN T, GUO X, et al. Sorafenib versus apatinib both combined transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis: A comparative retrospective study[J]. Front Oncol, 2021, 11: 673378. DOI: 10.3389/fonc.2021.673378.
[25]	QIU Z, SHEN L, JIANG Y, et al. Transarterial chemoembolization (TACE) combined with apatinib versus TACE combined with sorafenib in advanced hepatocellular carcinoma patients: a multicenter retrospective study[J]. Ann Transl Med, 2021, 9(4): 283. DOI: 10.21037/atm-20-5360.
[26]	GUO W, CHEN S, WU Z, et al. Efficacy and safety of transarterial chemoembolization combined with anlotinib for unresectable hepatocellular carcinoma: A retrospective study[J]. Technol Cancer Res Treat, 2020, 19: 1533033820965587. DOI: 10.1177/1533033820965587.
[27]	TURPIN A, de BAERE T, HEURGUÉ A, et al. Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study[J]. Clin Res Hepatol Gastroenterol, 2021, 45(2): 101464. DOI: 10.1016/j.clinre.2020.05.012.
[28]	XU Q, HUANG Y, SHI H, et al. Sunitinib versus sorafenib plus transarterial chemoembolization for inoperable hepatocellular carcinoma patients[J]. J BUON, 2018, 23(1): 193-199.
[29]	CHAN SL, YEO W, MO F, et al. A phase 2 study of the efficacy and biomarker on the combination of transarterial chemoembolization and axitinib in the treatment of inoperable hepatocellular carcinoma[J]. Cancer, 2017, 123(20): 3977-3985. DOI: 10.1002/cncr.30825.
[30]	ZHANG S, ZHAO Y, HE L, et al. Effect of camrelizumab plus transarterial chemoembolization on massive hepatocellular carcinoma[J]. Clin Res Hepatol Gastroenterol, 2022, 46(4): 101851. DOI: 10.1016/j.clinre.2021.101851.
[31]	YU SL, LIU DH, WANG C, et al. TACE combined with camrelizumab for treatment of advanced hepatocellular carcinoma[J]. Chin J Interv Imaging Ther, 2022, 19(7): 391-395. DOI: 10.13929/j.issn.1672-8475.2022.07.003. 于士龙, 刘东辉, 王储, 等. TACE联合卡瑞利珠单抗治疗中晚期肝细胞癌[J]. 中国介入影像与治疗学, 2022, 19(7): 391-395. DOI: 10.13929/j.issn.1672-8475.2022.07.003.
[32]	MOU L, TIAN X, ZHOU B, et al. Improving outcomes of tyrosine kinase inhibitors in hepatocellular carcinoma: New data and ongoing trials[J]. Front Oncol, 2021, 11: 752725. DOI: 10.3389/fonc.2021.752725.
[33]	ZHANG X, ZHU X, LIU C, et al. The safety and efficacy of transarterial chemoembolization (TACE) + lenvatinib + programmed cell death protein 1 (PD-1) antibody of advanced unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2022, 40(4_suppl): 453-453. DOI: 10.1200/JCO.2022.40.4_suppl.453
[34]	LI W, PEI Y, WANG Z, et al. Efficacy of transarterial chemoembolization monotherapy or combination conversion therapy in unresectable hepatocellular carcinoma: A systematic review and meta-analysis[J]. Front Oncol, 2022, 12: 930868. DOI: 10.3389/fonc.2022.930868.
[35]	LLOVET JM, VOGEL A, MADOFF DC, et al. Randomized phase 3 LEAP-012 study: Transarterial chemoembolization with or without lenvatinib plus pembrolizumab for intermediate-stage hepatocellular carcinoma not amenable to curative treatment[J]. Cardiovasc Intervent Radiol, 2022, 45(4): 405-412. DOI: 10.1007/s00270-021-03031-9.
[36]	WANG K, YU HM, XIANG YJ, et al. Transcatheter arterial chemoembolization plus atezolizumab and bevacizumab for unresectable hepatocellular carcinoma: a single-arm, phase Ⅱ trial[J]. Future Oncol, 2022, 18(30): 3367-3375. DOI: 10.2217/fon-2022-0188.

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Research advances in transcatheter arterial chemoembolization combined with targeted agents or anti-PD-1/PD-L1 monoclonal antibody in treatment of patients with unresectable hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2023.07.033

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Research advances in transcatheter arterial chemoembolization combined with targeted agents or anti-PD-1/PD-L1 monoclonal antibody in treatment of patients with unresectable hepatocellular carcinoma

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