Recent updates in intra-arterial therapy for hepatocellular carcinoma

doi:10.3877/cma.j.issn.2095-5782.2022.03.012

Abstract

Abstract:

Intra-arterial therapy is crucial for the treatment of unresectable hepatocellular carcinoma (HCC), and transarterial chemoembolization (TACE) is the most widely used method currently. In recent years, both hepatic arterial infusion chemotherapy (HAIC) and transarterial radioembolization (TARE) have gradually attracted attention, and have achieved gratifying curative effects in the treatment of advanced HCC. At the same time, with the emergence of more and more targeted and immunotherapy drugs, the treatment of HCC has entered the era of systemic therapy, which has greatly changed the treatment of HCC. The survival benefit and scheme exploration of intra-arterial therapy combined with systemic therapy are also being continuously paid attention by clinicians. This article aims to review the latest research progress of TACE, HAIC and TARE, which are commonly used in intra-arterial therapy.

Key words: Hepatocellular carcinoma, Intra-arterial therapy, Transarterial chemoembolization, Hepatic arterial infusion chemotherapy, Transarterial radioembolization

Tongqiang Li, Qin Shi, Bin Xiong. Recent updates in intra-arterial therapy for hepatocellular carcinoma[J]. Chinese Journal of Interventional Radiology(Electronic Edition), 2022, 10(03): 283-295.

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References 126

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研究者	时间	研究设计	队列	生存获益
Chao et al^[50]	2015	前瞻性、单臂、多中心研究	索拉非尼+ TACE（n = 192）	PFS：384 d
Lencioni et al^[32]	2016	随机、双盲、安慰剂对照、多中心、Ⅱ期研究	索拉非尼+ TACE（n = 154） vs安慰剂+ TACE（n = 154）	TTP：169 vs 166 d，P = 0.072
Meyer et al^[33]	2017	随机、双盲、安慰剂对照、多中心、Ⅲ期研究	索拉非尼+ TACE（n = 157） vs安慰剂+ TACE（n = 156）	PFS：120 vs 162d，P = 0.94
Kudo et al^[34]	2014	随机、双盲、安慰剂对照、多中心、Ⅲ期研究	布立尼布+ TACE（n = 249） vs安慰剂+ TACE（n = 253）	OS：26.4 vs 26.1个月，P = 0.528
Kudo et al^[35]	2017	随机、双盲、安慰剂对照、多中心、Ⅲ期研究	奥兰替尼+ TACE（n = 444） vs安慰剂+ TACE（n = 444）	OS：31.1 vs 32.3个月，P = 0.435
Kudo et al^[37]	2020	随机、多中心，Ⅱ期	索拉非尼+ TACE（n = 80） vs TACE（n = 76）	PFS：25.2 vs 13.5个月，P = 0.006
Ding et al^[51]	2021	随机、单中心、开放标签、对照研究	仑伐替尼+ TACE（n = 32） vs索拉非尼+TACE（n = 32）	ORR：53.1% vs 25.0%，P = 0.039 TTP：4.7 vs 3.1个月，P = 0.029
Chen et al^[44]	2021	多中心、回顾性研究	派姆单抗+仑伐替尼+ TACE（n = 70） vs仑伐替尼+ TACE（n = 72）	OS：18.1 vs 14.1个月，P = 0.004 PFS：9.2 vs 5.5个月，P = 0.006 ORR：47.1% vs 27.8%，P = 0.017 DCR：70.0% vs 52.8%，P = 0.036
Zheng et al^[45]	2021	回顾性研究	索拉非尼+ ICI + TACE（n = 22） vs索拉非尼+ TACE（n = 29）	OS：23.3 vs 13.8个月，P = 0.012 PFS：16.3 vs 7.3个月，P < 0.001 DCR：81.82% vs 55.17%，P = 0.046
Ju et al^[42]	2022	回顾性研究	阿帕替尼+卡瑞利珠单抗+ TACE（n = 56） vs阿帕替尼+卡瑞利珠单抗（n = 52）	OS：24.8 vs 13.1个月，P = 0.005 ORR：42.9% vs 17.3%，P = 0.004 DCR：85.7% vs 57.7%，P = 0.001
Cai et al^[43]	2022	回顾性研究	仑伐替尼+ ICI + TACE（n = 41） vs仑伐替尼+ TACE（n = 40）	OS：16.9 vs 12.1个月，P = 0.009 PFS：7.3 vs 4.0个月，P = 0.002 ORR：56.1% vs 32.5%，P = 0.033 DCR：85.4% vs 62.5%，P = 0.019
Facciorusso et al^[52]	2020	回顾性研究	TARE +索拉非尼（n = 45） vs索拉非尼（n = 90）	OS：10.0 vs 10.0个月，P = 0.711 PFS：6.0 vs 7.0个月，P = 0.992 ORR：45.5% vs 42.8%，P = 1
Ricke et al^[53]	2019	随机、对照研究	TARE +索拉非尼（n = 216） vs索拉非尼（n = 208）	OS：12.1 vs 11.4个月，P = 0.953

研究者	时间	研究设计	队列	生存获益
Chao et al^[50]	2015	前瞻性、单臂、多中心研究	索拉非尼+ TACE（n = 192）	PFS：384 d
Lencioni et al^[32]	2016	随机、双盲、安慰剂对照、多中心、Ⅱ期研究	索拉非尼+ TACE（n = 154） vs安慰剂+ TACE（n = 154）	TTP：169 vs 166 d，P = 0.072
Meyer et al^[33]	2017	随机、双盲、安慰剂对照、多中心、Ⅲ期研究	索拉非尼+ TACE（n = 157） vs安慰剂+ TACE（n = 156）	PFS：120 vs 162d，P = 0.94
Kudo et al^[34]	2014	随机、双盲、安慰剂对照、多中心、Ⅲ期研究	布立尼布+ TACE（n = 249） vs安慰剂+ TACE（n = 253）	OS：26.4 vs 26.1个月，P = 0.528
Kudo et al^[35]	2017	随机、双盲、安慰剂对照、多中心、Ⅲ期研究	奥兰替尼+ TACE（n = 444） vs安慰剂+ TACE（n = 444）	OS：31.1 vs 32.3个月，P = 0.435
Kudo et al^[37]	2020	随机、多中心，Ⅱ期	索拉非尼+ TACE（n = 80） vs TACE（n = 76）	PFS：25.2 vs 13.5个月，P = 0.006
Ding et al^[51]	2021	随机、单中心、开放标签、对照研究	仑伐替尼+ TACE（n = 32） vs索拉非尼+TACE（n = 32）	ORR：53.1% vs 25.0%，P = 0.039 TTP：4.7 vs 3.1个月，P = 0.029
Chen et al^[44]	2021	多中心、回顾性研究	派姆单抗+仑伐替尼+ TACE（n = 70） vs仑伐替尼+ TACE（n = 72）	OS：18.1 vs 14.1个月，P = 0.004 PFS：9.2 vs 5.5个月，P = 0.006 ORR：47.1% vs 27.8%，P = 0.017 DCR：70.0% vs 52.8%，P = 0.036
Zheng et al^[45]	2021	回顾性研究	索拉非尼+ ICI + TACE（n = 22） vs索拉非尼+ TACE（n = 29）	OS：23.3 vs 13.8个月，P = 0.012 PFS：16.3 vs 7.3个月，P < 0.001 DCR：81.82% vs 55.17%，P = 0.046
Ju et al^[42]	2022	回顾性研究	阿帕替尼+卡瑞利珠单抗+ TACE（n = 56） vs阿帕替尼+卡瑞利珠单抗（n = 52）	OS：24.8 vs 13.1个月，P = 0.005 ORR：42.9% vs 17.3%，P = 0.004 DCR：85.7% vs 57.7%，P = 0.001
Cai et al^[43]	2022	回顾性研究	仑伐替尼+ ICI + TACE（n = 41） vs仑伐替尼+ TACE（n = 40）	OS：16.9 vs 12.1个月，P = 0.009 PFS：7.3 vs 4.0个月，P = 0.002 ORR：56.1% vs 32.5%，P = 0.033 DCR：85.4% vs 62.5%，P = 0.019
Facciorusso et al^[52]	2020	回顾性研究	TARE +索拉非尼（n = 45） vs索拉非尼（n = 90）	OS：10.0 vs 10.0个月，P = 0.711 PFS：6.0 vs 7.0个月，P = 0.992 ORR：45.5% vs 42.8%，P = 1
Ricke et al^[53]	2019	随机、对照研究	TARE +索拉非尼（n = 216） vs索拉非尼（n = 208）	OS：12.1 vs 11.4个月，P = 0.953

研究者	时间	研究人群	研究设计	生存获益
Tong Y et al^[56]	2017	术后辅助治疗	手术+ TACE（n = 83） vs单纯手术（n = 83）	1/3/5年OS：100%、91.5%、83.3% vs 97.6%、84.8%、78.2%，P = 0.995； 1/3/5年RFS：87.5%、56.4%、50.0% vs 90.4%、64.3%、51.6%, P = 0.297
Jiang et al^[60]	2015	术后辅助化疗	手术+ TACE（n = 91） vs单纯手术（n = 138）	1/2/3年OS：95.1%、86.7%、76.4% vs 86.9%、78.5%、73.2%, P = 0.543； 1/3/5年RFS：86.6%、69.4%、59.9% vs 75.2%、67.9%、66.0%, P = 0.425
Xie et al^[61]	2019	术后辅助治疗	手术+ TACE（n = 102） vs单纯手术（n = 78）	PFS：52.0 vs 11.1个月，P< 0.001； OS：90.7 vs 54.4个月，P< 0.001
Sun et al^[57]	2016	伴MVI肝癌术后辅助治疗	手术+ TACE（n = 137） vs单纯手术（n = 185）	1/3/5年OS：94.2%、71.5%、54.0 %，vs 78.9%、54.1%、43.2%，P = 0.012; 1/3/5年RFS：69.3%、46.7%、35.0% vs 47.0%、34.1%、30.3%，P = 0.006;
Wang et al^[55]	2018	HBV相关肝癌术后辅助化疗	手术+ TACE（n = 140） vs单纯手术（n = 140）	RFS：49.5 vs 23.8个月，P = 0.01； 3年OS：85.2% vs 77.4%，P = 0.04
Ye et al^[58]	2017	伴或不伴MVI术后辅助治疗	手术+ TACE（n = 158） vs单纯手术（n = 361）	伴MVI： 1/2/3/4年OS：92.7%、86.5%、73.1%、67.5% vs 81.3%、65.7%、58.8%、53.9%，P = 0.019；不伴MVI： 1/2/3/4年OS：94.2%、91.9%、87.6%、87.6% vs 98.8%、91.5%、82.8%、82.8%，P = 0.872； 1/2/3/4年RFS：83.0%、71.8%、61.9%、不可用vs 80.7%、70.1%、61.2%、55.9%，P = 0.974

研究者	时间	研究人群	研究设计	生存获益
Tong Y et al^[56]	2017	术后辅助治疗	手术+ TACE（n = 83） vs单纯手术（n = 83）	1/3/5年OS：100%、91.5%、83.3% vs 97.6%、84.8%、78.2%，P = 0.995； 1/3/5年RFS：87.5%、56.4%、50.0% vs 90.4%、64.3%、51.6%, P = 0.297
Jiang et al^[60]	2015	术后辅助化疗	手术+ TACE（n = 91） vs单纯手术（n = 138）	1/2/3年OS：95.1%、86.7%、76.4% vs 86.9%、78.5%、73.2%, P = 0.543； 1/3/5年RFS：86.6%、69.4%、59.9% vs 75.2%、67.9%、66.0%, P = 0.425
Xie et al^[61]	2019	术后辅助治疗	手术+ TACE（n = 102） vs单纯手术（n = 78）	PFS：52.0 vs 11.1个月，P< 0.001； OS：90.7 vs 54.4个月，P< 0.001
Sun et al^[57]	2016	伴MVI肝癌术后辅助治疗	手术+ TACE（n = 137） vs单纯手术（n = 185）	1/3/5年OS：94.2%、71.5%、54.0 %，vs 78.9%、54.1%、43.2%，P = 0.012; 1/3/5年RFS：69.3%、46.7%、35.0% vs 47.0%、34.1%、30.3%，P = 0.006;
Wang et al^[55]	2018	HBV相关肝癌术后辅助化疗	手术+ TACE（n = 140） vs单纯手术（n = 140）	RFS：49.5 vs 23.8个月，P = 0.01； 3年OS：85.2% vs 77.4%，P = 0.04
Ye et al^[58]	2017	伴或不伴MVI术后辅助治疗	手术+ TACE（n = 158） vs单纯手术（n = 361）	伴MVI： 1/2/3/4年OS：92.7%、86.5%、73.1%、67.5% vs 81.3%、65.7%、58.8%、53.9%，P = 0.019；不伴MVI： 1/2/3/4年OS：94.2%、91.9%、87.6%、87.6% vs 98.8%、91.5%、82.8%、82.8%，P = 0.872； 1/2/3/4年RFS：83.0%、71.8%、61.9%、不可用vs 80.7%、70.1%、61.2%、55.9%，P = 0.974

研究者	时间	研究设计	药物方案	研究人群	疗效评价
Ikeda et al^[79]	2013	单臂、多中心、Ⅱ期研究	顺铂（65 mg/m²），团注；	伴PVT患者（n = 25）	ORR：28.0% PFS：3.6个月 OS：7.6个月
Chen et al^[88]	2020	前瞻性、单臂、Ⅱ期研究	奥沙利铂（100 mg/m²，连续输注4 h）和雷替曲塞（3 mg/m²，连续输注1 h）	伴有PVT的TACE难治性患者（n = 39）	ORR：46.2%
Kawaoka et al^[80]	2018	回顾性研究	5-FU：低剂量顺铂（6 mg/d）+5-氟尿嘧啶（300 mg/d），连续输注；顺铂：65 mg/m²，团注	5-FU（n = 102） vs顺铂（n = 51）	ORR：32.4% vs 15.7%，P = 0.033 OS：9.1 vs 8.7个月，P = 0.4917 PFS：3.9 vs 4.9个月，P = 0.4
Song et al^[89]	2015	多中心回顾性研究	HAIC：5-氟尿嘧啶（第1~3天500 mg/m²，5 h）+顺铂（第2天60 mg/m²，2 h），加或不加表柔比星（第1天35 mg/m²）；索拉非尼：400 mg/d；伴PVT患者	HAIC（n = 50） vs索拉非尼（n = 60）	OS：7.1 vs 5.1个月，P = 0.011 TTP：3.3 vs 2.1个月，P = 0.034 DCR：90% vs 45%，P < 0.001 ORR：24.0% vs 13.3%，P = 0.214
Choi et al^[90]	2018	随机、对照、多中心、前瞻性研究	HAIC：5-氟尿嘧啶（第1~3天500 mg/m²，5 h）+顺铂（第2天60 mg/m²，2 h）；索拉非尼：800 mg/d；伴PVT患者	HAIC（n = 29） vs索拉非尼（n = 29）	OS：14.9 vs 7.2个月，P = 0.012 TTP：4.4 vs 2.7个月，P = 0.010 ORR：27.6% vs 3.4%，P < 0.001
Lyu et al^[84]	2018	回顾性研究	FOLFOX-HAIC：奥沙利铂，130 mg/m²，3 h；亚叶酸：200 mg/m²，2 h；氟尿嘧啶：400 mg/m²团注，后2 400 mg/m²连续输注46 h；索拉非尼：400 mg/d	HAIC（n = 180） vs索拉非尼（n = 232）	OS：14.5 vs 7.0个月，P < 0.001 PFS：7.1 vs 3.3个月，P < 0.001 ORR：47.8% vs 9.1%，P < 0.001 DCR：79.4% vs 51.7%，P < 0.001
Lyu et al^[91]	2022	前瞻性、随机、Ⅲ期研究	FOLFOX-HAIC：同上；索拉非尼：400 mg/d	HAIC（n = 130） vs索拉非尼（n = 132）	OS：13.9 vs 8.2个月，P < 0.001 ORR：31.5% vs 1.5%，P < 0.001
Kudo et al^[86]	2018	随机、开放标签、多中心研究	HAIC：顺铂：20 mg/m²，第1与第8天5-氟尿嘧啶：330 mg/m²，第1~5天与第8~12天，连续输注；索拉非尼：400 mg/d；	索拉非尼+HAIC（n = 103） vs索拉非尼（n = 103）	OS：11.8 vs 11.5个月，P = 0.955
Ikeda et al^[92]	2016	随机、开放标签、多中心、Ⅱ期试验	HAIC：顺铂（65 mg/m²），团注；索拉非尼：400 mg/d	索拉非尼+HAIC（n = 66） vs索拉非尼（n = 42）	OS：10.6 vs 8.7个月，P = 0.031
He et al^[93]	2019	随机、开放标签、多中心研究	mFOLFOX-HAIC：奥沙利铂，85 mg/m²，2 h；亚叶酸，400 mg/m²，1 h；氟尿嘧啶，400 mg/m²团注，后2 400 mg/m²超过46 h；索拉非尼：400 mg/d；伴PVT患者	索拉非尼+HAIC（n = 125） vs索拉非尼（n = 122）	OS：13.4 vs 7.1个月，P < 0.001 PFS：7.0 vs 2.6个月，P < 0.001 ORR：40.8% vs 2.46%，P < 0.001
Liang et al^[94]	2021	回顾性研究	mFOLFOX-HAIC：同上；索拉非尼：400 mg/d	索拉非尼+HAIC（n = 99） vs HAIC（n = 126）	OS：12.9 vs 10.5个月，P = 0.025 PFS：7.0 vs 5.3个月，P = 0.046 DCR：74.8% vs 61.1%，P = 0.030
He et al^[85]	2017	前瞻性、非随机、Ⅱ期研究	mFOLFOX-HAIC：同上；cTACE：50 mg表柔比星+ 50 mg洛铂+6 mg丝裂霉素C+碘油	HAIC（n = 38） vs cTACE（n = 41）	ORR：52.6% vs 9.8%，P < 0.001 DCR：83.8% vs 52.5%，P = 0.004 TTP：5.87 vs 3.6个月，P = 0.015
Li et al^[95]	2022	前瞻性、随机、多中心、开放标签、Ⅲ期研究	FOLFOX-HAIC：同上；cTACE：50 mg表柔比星+ 50 mg洛铂+碘油，肿瘤> 7 cm；	HAIC（n = 159） vs cTACE（n = 156）	OS：23.1 vs 16.1个月，P < 0.001 PFS：9.6 vs 5.4个月，P < 0.001 ORR：46.0% vs 18.0%，P < 0.001

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