肝细胞癌的转化治疗中几个重要却尚无答案的问题

doi:10.16139/j.1007-9610.2024.02.03

摘要/Abstract

摘要：

靶向药物和免疫检查点抑制剂等系统治疗显著提高了晚期不可切除肝细胞癌病人的预后，但仍难以达到长期生存。转化治疗作为系统治疗与外科治疗结合的主要方向之一，使部分不可切除的肝细胞癌病人获得根治性切除与治愈的机会，近年在国内不同中心广泛开展，并在2021年发布首个《肝癌转化治疗中国专家共识》。同时应看到，在肝癌转化治疗的理论与实践中，还存在诸多关键性问题，目前尚无充足的循证证据回答。积极思考、探索并最终回答这些问题，对于建立、推广肝癌转化治疗的标准化理论体系至关重要。

关键词: 肝细胞癌, 转化治疗, 靶向治疗, 免疫检查点抑制剂, 系统性治疗, 手术切除

Abstract:

Progress in the systemic therapies, represented by the molecular target therapies and immune checkpoint inhibitors (ICIs), have significantly improved the prognosis of unresectable hepatocellular carcinoma (uHCC), but long term survial remains limitted. As one of the major combination of systemic and surgical therapies, conversion therapy provides potentially curative opportunity to some uHCC patients. It is widely reported from different domestic centers.The first Chinese expert consensus about it was released in 2021. Yet at the same time, there are many key issues in the practice and theory remains to be resolved. Actively thinking, exploring and finally resolving these issues are essential for establishing and promoting the standardized theoretical system of uHCC conversion therapy.

Key words: Hepatocellular carcinoma, Conversion therapy, Target therapy, Immune checkpoint inhibitor (ICI), Systemic therapy, Surgical resection

中图分类号:

R735.7

赵磊, 钟敬涛, 孙惠川. 肝细胞癌的转化治疗中几个重要却尚无答案的问题[J]. 外科理论与实践, 2024, 29(02): 106-113.

ZHAO Lei, ZHONG Jingtao, SUN Huichuan. Conversion therapy of hepatocellular carcinoma: some pivotal issues to be resolved[J]. Journal of Surgery Concepts & Practice, 2024, 29(02): 106-113.

图/表 2

表1

HCC免疫靶向治疗临床试验结果

肝癌免疫联合靶向药物治疗的相关临床研究
序号	试验名称	联合组药物	对照组药物	试验分期	治疗线数	结果
1	IMbrave150^[17]	阿替利珠单抗+贝伐珠单抗	索拉非尼	Ⅲ期	一线治疗	mPFS:6.9个月比4.3个月 mOS:19.2个月比13.4个月
2	ORIENT-32^[18]	信迪利单抗+贝伐珠单抗	索拉非尼	Ⅲ期	一线治疗	mPFS:4.6个月比2.8个月 mOS:NE比10.4个月
3	SHR-1210-Ⅲ-310^[19]	卡瑞利珠单抗+阿帕替尼	索拉非尼	Ⅲ期	一线治疗	mPFS:5.6个月比 3.7个月 mOS:22.1个月比15.2个月
4	Leap-002^[20]	帕博利珠单抗+仑伐替尼	仑伐替尼	Ⅲ期	一线治疗	mPFS:8.2个月比8.0个月 mOS:21.2个月比19.0个月
5	COSMIC-312^[21]	阿替利珠单抗+卡博替尼	索拉非尼	Ⅲ期	一线治疗	mPFS:6.8个月比4.2个月 mOS:15.4个月比15.5个月
6	NCT04052152 KEEP-G04^[22]	信迪利单抗+安罗替尼		Ⅱ 期	一线治疗	ORR：35.0%（RECIST v1.1） ORR：55.0%（mRECIST） mPFS：12.2 个月
7	NCT03347292	瑞戈非尼+帕博利珠单抗		Ib期	一线治疗	120 mg瑞戈非尼，ORR=31%，DCR=88% 80 mg瑞戈非尼，ORR=18%，DCR=91%
8	ALTER-H003	安罗替尼+特瑞普利单抗		Ⅱ期	一线治疗	ORR和DCR分别为32.3% 和77.4%(mRECIST) mPFS：11.0个月 mOS：18.2个月
9	NCT04444167^[23]	AK104（PD-1/CTLA-4双特异性抗体）+仑伐替尼		Ⅱ期	一线治疗	A队列（AK104 6 mg/kg, Q2W）比 B队列（AK104 15 mg/kg, Q3W） ORR：35.5%比35.7% mPFS：8.61个月比9.82个月 mOS：27.1个月比NR
10	IMMUNIB	纳武利尤单抗+仑伐替尼		Ⅱ期	一线治疗	ORR：28% mPFS：7.06个月 mOS：27.1个月
11	NCT04542837	KN046(抗PD-L1/CTLA-4双特异性抗体)+仑伐替尼		Ⅱ期	一线治疗	ORR：51.9%(RECIST v1.1) DCR：86.5%(RECIST v1.1) mPFS：9.3个月；mOS尚未达到
12	NCT03289533^[24]	阿维鲁单抗+阿西替尼		Ib期	一线治疗	ORR:31.8%(mRECIST)/13.6%(RECIST1.1) DCR:68.2%(mRECIST)/68.2%(RECIST1.1)

表1

图1

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