开放期刊系统

TACE 联合靶向或免疫药物治疗中晚期肝细胞癌的研究进展

李 国良, 赵 得武, 潘 彪, 王海 久*

摘要

原发性肝癌(primary carcinoma of liver)主要包括肝细胞癌(HCC)、肝内胆管癌(ICC)和混合型肝细胞癌 -
胆管癌(cHCC-CCA)三种不同病理学类型,其中 HCC 占 75%~85%,最为多见。HCC 的全球发病率上升和死亡率居高
不下,要求我们采取紧急和创新的措施来改善患者的预后。随着近些年靶免治疗的兴起,通过治疗方式的改进,较大程度
降低了 HCC 患者死亡率,并改善了患者生活质量。在本综述中,我们论述了 TACE 联合靶向以及 TACE 联合免疫治疗中
晚期 HCC 的最新研究成果,涵盖了联合治疗策略的临床证据,以及探索了未来 TACE 联合治疗在未来为肝癌患者提供个
性化的综合治疗方案,提高患者生存期的潜力。

关键词

TACE;靶向治疗;免疫治疗;肝细胞癌

全文:

PDF

参考

[1] Sung H, Ferlay J, Siegel R L, 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.

[2] Forner A, Reig M, Bruix J. Hepatocellular carcinoma[J].

Lancet,2018,391(10127):1301-1314.

[3] EASL Clinical Practice Guidelines: Management of

hepatocellular carcinoma[J]. J Hepatol,2018,69(1):182-236.

[4] 中华人民共和国国家卫生健康委员会 . 原发性肝癌

诊疗指南 (2024 年版 )[J]. 临床肝胆病杂志 ,2024,40(5):893-918.

[5] Wang B, Xu H, Gao Z Q, et al. Increased expression of

vascular endothelial growth factor in hepatocellular carcinoma

after transcatheter arterial chemoembolization[J]. Acta

Radiol,2008,49(5):523-529.

[6] Liu Y, Cao X. Immunosuppressive cells in tumor immune

escape and metastasis[J]. J Mol Med (Berl),2016,94(5):509-522.

[7] Yap T A, Parkes E E, Peng W, et al. Development of

Immunotherapy Combination Strategies in Cancer[J]. Cancer

Discov,2021,11(6):1368-1397.

[8] EASL-EORTC clinical practice guidelines: management

of hepatocellular carcinoma[J]. J Hepatol,2012,56(4):908-943.

[9] Llovet J M, Bruix J. Systematic review of randomized trials

for unresectable hepatocellular carcinoma: Chemoembolization

improves survival[J]. Hepatology,2003,37(2):429-442.

[10] Han G, Berhane S, Toyoda H, et al. Prediction of Survival

Among Patients Receiving Transarterial Chemoembolization for

Hepatocellular Carcinoma: A Response-Based Approach[J].

Hepatology,2020,72(1):198-212.

[11] Schicho A, Hellerbrand C, Kruger 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.

[12] Greten T F, Korangy F, Manns M P, et al. Molecular

therapy for the treatment of hepatocellular carcinoma[J]. Br J

Cancer,2009,100(1):19-23.

[13] Koch C, Goller M, Schott E, et al. Combination of

Sorafenib and Transarterial Chemoembolization in Selected

Patients with Advanced-Stage Hepatocellular Carcinoma: A

Retrospective Cohort Study at Three German Liver Centers[J].

Cancers (Basel),2021,13(9).

[14] Zhao Y, Wang W J, Guan S, et al. Sorafenib combined

with transarterial chemoembolization for the treatment of

advanced hepatocellular carcinoma: a large-scale multicenter

study of 222 patients[J]. Ann Oncol,2013,24(7):1786-1792.

[15] Kawamura Y, Kobayashi M, Shindoh J, et al.

Lenvatinib-Transarterial Chemoembolization Sequential Therapy

as an Effective Treatment at Progression during Lenvatinib

Therapy for Advanced Hepatocellular Carcinoma[J]. Liver

Cancer,2020,9(6):756-770.

[16] Liu K C, Hao Y H, Lv W F, et al. Transarterial

Chemoembolization Combined with Sorafenib in Patients with

BCLC Stage C Hepatocellular Carcinoma[J]. Drug Des Devel

Ther,2020,14:3461-3468.

[ 1 7 ] L e e S W , L e e T Y , P e n g Y C , e t a l . T h e

therapeutic benefits of combined sorafenib and transarterial

chemoembolization for advanced hepatocellular carcinoma[J]. J

Dig Dis,2020,21(5):287-292.

[18] Varghese J, Kedarisetty C, Venkataraman J, et al.

Combination of TACE and Sorafenib Improves Outcomes in

BCLC Stages B/C of Hepatocellular Carcinoma: A Single Centre

Experience[J]. Ann Hepatol,2017,16(2):247-254.

[19] 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.

[20] Chen R, Li L, Li Y, et al. Efficacy and safety of

transcatheter arterial chemoembolization-lenvatinib sequential

therapy for patients with unresectable hepatocellular

carcinoma: a single-arm clinical study[J]. J Gastrointest

Oncol,2022,13(3):1367-1375.

[21] Cheon J, Chon H J, Bang Y, et al. Real-World Efficacy

and Safety of Lenvatinib in Korean Patients with Advanced

Hepatocellular Carcinoma: A Multicenter Retrospective

Analysis[J]. Liver Cancer,2020,9(5):613-624.

[22] Peng Z, Fan W, Zhu B, et al. Lenvatinib Combined With

Transarterial Chemoembolization as First-Line Treatment for

Advanced Hepatocellular Carcinoma: A Phase III, Randomized

Clinical Trial (LAUNCH)[J]. J Clin Oncol,2023,41(1):117-127.

[23] Matsuda N, Imai N, Kuzuya T, et al. Progression

After Molecular Targeted Agents: Hepatic Arterial Changes and

Transarterial Chemoembolization in Hepatocellular Carcinoma[J].

In Vivo,2021,35(2):1185-1189.

[24] Rimassa L, Pressiani T, Personeni N, et al. Regorafenib

for the treatment of unresectable hepatocellular carcinoma[J].

Expert Rev Anticancer Ther,2017,17(7):567-576.

[25] Mross K, Frost A, Steinbild S, et al. A phase I dose-

escalation study of regorafenib (BAY 73-4506), an inhibitor

of oncogenic, angiogenic, and stromal kinases, in patients with

advanced solid tumors[J]. Clin Cancer Res,2012,18(9):2658-

2667.

[26] Choi G H, Shim J H, Kim M J, et al. Sorafenib alone

versus sorafenib combined with transarterial chemoembolization

for advanced-stage hepatocellular carcinoma: results of propensity

score analyses[J]. Radiology,2013,269(2):603-611.

[27] Wang H, Xiao W, Han Y, et al. Study on safety and

efficacy of regorafenib combined with transcatheter arterial

chemoembolization in the treatment of advanced hepatocellular

carcinoma after first-line targeted therapy[J]. J Gastrointest

Oncol,2022,13(3):1248-1254.

[28] Bao Y, Feng W M, Tang C W, et al. Endostatin

inhibits angiogenesis in hepatocellular carcinoma after

transarterial chemoembolization[J]. Hepatogastroenterolo

gy,2012,59(117):1566-1568.

[29] Wei F, Zhong S, Ma Z, et al. Strength of PD-1 signaling

differentially affects T-cell effector functions[J]. Proc Natl Acad

Sci U S A,2013,110(27):E2480-E2489.

[30] Strome S E, Dong H, Tamura H, et al. B7-H1 blockade

augments adoptive T-cell immunotherapy for squamous cell

carcinoma[J]. Cancer Res,2003,63(19):6501-6505.

[31] Bai J, Liang P, Li Q, et al. Cancer Immunotherapy -

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma[J].

Recent Pat Anticancer Drug Discov,2021,16(2):239-248.

[32] Whiteside T L, Demaria S, Rodriguez-Ruiz M

E, et al. Emerging Opportunities and Challenges in Cancer

Immunotherapy[J]. Clin Cancer Res,2016,22(8):1845-1855.

[33] Weber J S, D’Angelo S P, Minor D, et al. Nivolumab

versus chemotherapy in patients with advanced melanoma who

progressed after anti-CTLA-4 treatment (CheckMate 037): a

randomised, controlled, open-label, phase 3 trial[J]. Lancet

Oncol,2015,16(4):375-384.

[34] Motzer R J, Escudier B, Mcdermott D F, et al. Nivolumab

versus Everolimus in Advanced Renal-Cell Carcinoma[J]. N Engl

J Med,2015,373(19):1803-1813.

[35] Topalian S L, Drake C G, Pardoll D M. Immune

checkpoint blockade: a common denominator approach to cancer

therapy[J]. Cancer Cell,2015,27(4):450-461.

[36] Prieto J, Melero I, Sangro B. Immunological landscape

and immunotherapy of hepatocellular carcinoma[J]. Nat Rev

Gastroenterol Hepatol,2015,12(12):681-700.

[37] Flecken T, Schmidt N, Hild S, et al. Immunodominance

and functional alterations of tumor-associated antigen-specific

CD8+ T-cell responses in hepatocellular carcinoma[J]. Hepatolo

gy,2014,59(4):1415-1426.

[38] Shi F, Shi M, Zeng Z, et al. PD-1 and PD-L1

upregulation promotes CD8(+) T-cell apoptosis and postoperative

recurrence in hepatocellular carcinoma patients[J]. Int J

Cancer,2011,128(4):887-896.

[39] Breous E, Thimme R. Potential of immunotherapy for

hepatocellular carcinoma[J]. J Hepatol,2011,54(4):830-834.

[40] Llovet J M, Vogel A, Madoff D C, 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.

[41] Finn R S, Ikeda M, Zhu A X, et al. Phase Ib

Study of Lenvatinib Plus Pembrolizumab in Patients

With Unresectable Hepatocellular Carcinoma[J]. J Clin

Oncol,2020,38(26):2960-2970.

[42] Llovet J M, De Baere T, Kulik L, et al. Locoregional

therapies in the era of molecular and immune treatments

for hepatocellular carcinoma[J]. Nat Rev Gastroenterol

Hepatol,2021,18(5):293-313.

[43] Liu L, Zhang R, Deng J, et al. Construction of TME

and Identification of crosstalk between malignant cells and

macrophages by SPP1 in hepatocellular carcinoma[J]. Cancer

Immunol Immunother,2022,71(1):121-136.

[44] Liu Y, Xun Z, Ma K, et al. Identification of a tumour

immune barrier in the HCC microenvironment that determines the

efficacy of immunotherapy[J]. J Hepatol,2023,78(4):770-782.

[45] Yamauchi R, Ito T, Yoshio S, et al. Serum osteopontin

predicts the response to atezolizumab plus bevacizumab

in patients with hepatocellular carcinoma[J]. J Gastroenter

ol,2023,58(6):565-574.

[46] Pinato D J, Murray S M, Forner A, et al. Trans-arterial

chemoembolization as a loco-regional inducer of immunogenic

cell death in hepatocellular carcinoma: implications for

immunotherapy[J]. J Immunother Cancer,2021,9(9).

[47] Cheng Y, Spigel D R, Cho B C, et al. Durvalumab after

Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer[J].

N Engl J Med,2024,391(14):1313-1327.

[48] Riccardo Lencioni et al., EMERALD-1: A phase

3, randomized, placebo-controlled study of transarterial

chemoembolization combined with durvalumab with or without

bevacizumab in participants with unresectable hepatocellular

carcinoma eligible for embolization.. JCO 42, LBA432-

LBA432(2024).

[49] 姜楠,黄金涛,聂宏,等 . TACE 联合靶向免疫药

物治疗晚期肝细胞癌的有效性和安全性 [J]. 介入放射学杂

志 ,2023,32(5):441-445.

[50]Cheng Y, Spigel DR, Cho BC, Laktionov KK, Fang J,

Chen Y, Zenke Y, Lee KH, Wang Q, Navarro A, Bernabe R,

Buchmeier EL, Chang JW, Shiraishi Y, Goksu SS, Badzio A,

Shi A, Daniel DB, Hoa NTT, Zemanova M, Mann H, Gowda H,

Jiang H, Senan S; ADRIATIC Investigators. Durvalumab after

Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. N

Engl J Med. 2024 Oct 10;391(14):1313-1327.


(3 摘要 Views, 2 PDF Downloads)

Refbacks

  • 当前没有refback。