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中华肝脏外科手术学电子杂志 ›› 2025, Vol. 14 ›› Issue (04) : 554 -560. doi: 10.3877/cma.j.issn.2095-3232.2025.04.009

临床研究

TACE-HAIC联合仑伐替尼和PD-1抑制剂四联治疗Ⅲa期肝癌的疗效
匡嘉文, 陈铁军, 龚远锋, 唐辉, 唐云强†()   
  1. 510095　广州医科大学附属肿瘤医院肝胆外科
  • 收稿日期:2024-12-23 出版日期:2025-08-10
  • 通信作者: 唐云强
  • 基金资助:
    吴阶平医学基金会临床科研专项资助基金(320.6750.2022-01-8); 湖北陈孝平科技发展基金会(CXPJJH1200008-12)

Efficacy of TACE-HAIC combined with lenvatinib and PD-1 inhibitor in the treatment of stage Ⅲa liver cancer

Jiawen Kuang, Tiejun Chen, Yuanfeng Gong, Hui Tang, Yunqiang Tang†()   

  1. Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou 510095, China
  • Received:2024-12-23 Published:2025-08-10
  • Corresponding author: Yunqiang Tang
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引用本文：

匡嘉文, 陈铁军, 龚远锋, 唐辉, 唐云强. TACE-HAIC联合仑伐替尼和PD-1抑制剂四联治疗Ⅲa期肝癌的疗效[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(04): 554-560.

Jiawen Kuang, Tiejun Chen, Yuanfeng Gong, Hui Tang, Yunqiang Tang. Efficacy of TACE-HAIC combined with lenvatinib and PD-1 inhibitor in the treatment of stage Ⅲa liver cancer[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2025, 14(04): 554-560.

目的

探讨TACE-肝动脉灌注化疗（HAIC）联合仑伐替尼和PD-1抑制剂四联治疗Ⅲa期肝癌的疗效。

方法

回顾性分析2020年1月至2023年5月广州医科大学附属肿瘤医院收治的96例Ⅲa期肝癌患者临床资料。患者均签署知情同意书，符合医学伦理学规定。其中男86例，女10例；年龄33~74岁，中位年龄54岁。患者均为CNLC分期Ⅲa期。根据患者治疗方案不同，患者分为四联组（62例）和三联组（34例），四联组采用TACE-HAIC联合仑伐替尼和PD-1抑制剂，三联组采用TACE-HAIC联合仑伐替尼。采用1∶1倾向性评分匹配（PSM）获得组间均衡。此次研究设置主要研究终点为总生存期（OS）和无进展生存期（PFS）。两组不良反应的发生率等比较采用χ2检验或Fisher确切概率法。生存分析采用Kaplan-Meier法和Log-rank检验。生存影响因素分析采用Cox比例风险模型回归分析。

结果

PSM后四联组中位OS为32.0个月（95%CI：10.985~53.015），三联组14.0个月（95%CI：6.548~21.452），差异有统计学意义（χ2=9.071，P=0.003）。四联组中位PFS为19.0个月（95%CI：9.655~28.345），三联组6.0个月（95%CI：3.197~8.803），差异有统计学意义（χ2=7.811，P=0.005）。Cox回归分析显示，治疗方式（HR=0.318，95%CI：0.144~0.701；P=0.004）和TACE-HAIC次数（HR=0.415，95%CI：0.197~0.873；P=0.020）是影响OS的独立影响因素；治疗方式是PFS的独立影响因素（HR=0.439，95%CI：0.238~0.810；P=0.008）。本研究中未发生与毒性相关的死亡事件。在任何等级和3/4级不良反应中，2组发生率比较差异均无统计学意义（P>0.05）。

结论

TACE-HAIC联合仑伐替尼和PD-1抑制剂的四联治疗方案明显提高了Ⅲa期肝癌患者的生存获益，且不良反应发生率并未增加。

关键词: 癌，肝细胞, 血管侵犯, 仑伐替尼, PD-1抑制剂, 介入治疗, 经导管动脉化疗栓塞, 肝动脉灌注化疗, 生存分析
Objective

To evaluate the efficacy of TACE-hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and PD-1 inhibitor in the treatment of stage Ⅲa liver cancer.

Methods

Clinical data of 96 patients with stage Ⅲa liver cancer admitted to Cancer Hospital of Guangzhou Medical University from January 2020 to May 2023 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 86 patients were male and 10 female, aged from 33 to 74 years, with a median age of 54 years. All patients were classified as CNLC stage Ⅲa. According to different treatment protocols, all patients were divided into the quadruple-treatment group (n=62) and triple-treatment group (n=34). In the quadruple-treatment group, patients were treated with TACE-HAIC combined with lenvatinib and PD-1 inhibitor, and those in the triple-treatment group were treated with TACE-HAIC combined with lenvatinib. Inter-group equilibrium was obtained by 1∶1 propensity score matching (PSM). Primary end points were overall survival (OS) and progression-free survival (PFS). The incidence of adverse reactions between two groups was compared by Chi-square test or Fisher’s exact test. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The influencing factors of survival were identified by Cox proportional hazard regression model.

Results

After PSM, the median OS in the quadruple-treatment group was 32.0 months (95%CI: 10.985-53.015), and 14.0 months in the triple-treatment group (95%CI: 6.548-21.452), and the difference was statistically significant (χ2=9.071, P=0.003). The median PFS in the quadruple-treatment group was 19.0 months (95%CI: 9.655-28.345), and 6.0 months in the triple-treatment group (95%CI: 3.197-8.803), and the difference was statistically significant (χ2=7.811, P=0.005). Cox’s regression analysis showed that treatment method (HR=0.318, 95%CI: 0.144-0.701; P=0.004) and frequency of TACE-HAIC (HR=0.415, 95%CI: 0.197-0.873; P=0.020) were the independent influencing factors of OS. Treatment method was an independent influencing factor of PFS (HR=0.439, 95%CI: 0.238-0.810; P=0.008). No toxicity-related death occurred in this study. No significant difference was found in the incidence of any grade and grade 3/4 adverse reactions (all P>0.05).

Conclusions

The quadruple therapy of TACE-HAIC combined with lenvatinib and PD-1 inhibitor can significantly improve the survival benefit of patients with stage Ⅲa liver cancer without sacrificing the incidence of adverse reactions.

Key words: Carcinoma,hepatocellular, Vascular invasion, Lenvatinib, PD-1 inhibitor, Interventional therapy, Transcatheter arterial chemoembolization, Hepatic artery infusion chemotherapy, Survival analysis
表1 PSM前后两组肝癌患者基线资料比较
变量 PSM前 PSM后
四联组 三联组 统计值 P值 四联组 三联组 统计值 P值
男性(例) 54 32 χ2=1.160 0.281 29 31 χ2=0.733 0.392
年龄(岁,±s) 53±11 53±11 t=0.044 0.965 52±9 53±11 t=-0.461 0.647
肿瘤直径≥10 cm(例) 34 15 χ2=1.010 0.315 14 15 χ2=0.062 0.804
AFP≥400 μg/L(例) 43 22 χ2=0.217 0.641 23 22 χ2=0.070 0.792
TACE-HAIC≥2次(例) 42 19 χ2=1.333 0.248 23 18 χ2=1.610 0.205
Hb≥120 g/L(例) 45 30 χ2=3.149 0.076 29 29 - -
WBC<4×109/L(例) 8 1 χ2=2.565 0.109 1 1 - -
Plt<100×109/L(例) 58 32 χ2=0.012 0.912 31 31 - -
ALB≥35 g/L(例) 30 18 χ2=0.182 0.670 20 17 χ2=0.554 0.457
AST>40 U/L(例) 52 25 χ2=1.479 0.224 26 25 χ2=0.086 0.769
ALT>50 U/L(例) 32 14 χ2=0.958 0.328 20 14 χ2=2.184 0.139
PT>13.2 s(例) 10 11 χ2=3.382 0.066 5 11 χ2=2.970 0.085
TB>17.1 μmol/L(例) 18 15 χ2=2.215 0.137 9 15 χ2=2.357 0.125
HBsAg阳性(例) 60 31 χ2=1.394 0.238 33 30 χ2=3.143 0.076
表2 四联组和三联组肝瘤患者治疗后肿瘤应答情况[例（%）]
治疗效果 四联组 三联组 χ2值 P值
CR 6(18) 0 6.600 0.010
PR 16(48) 9(27) 3.155 0.076
SD 2(6) 7(21) 3.216 0.073
PD 9(27) 17(52) 4.062 0.044
ORR 22(67) 9(27) 10.280 0.001
DCR 24(73) 16(48) 4.062 0.044
图1 四联组和三联组肝瘤患者Kaplan-Meier生存曲线注：PSM后两组均33例；四联组采用TACE-HAIC联合仑伐替尼和PD-1抑制剂治疗；三联组采用TACE-HAIC联合仑伐替尼治疗；HAIC为肝动脉灌注化疗，PSM为倾向性评分匹配
表3 四联组和三联组肝癌患者治疗相关不良反应发生情况（例）
不良反应 任何等级 等级3/4
四联组 三联组 χ2值 P值 四联组 三联组 χ2值 P值
低蛋白血症 26 28 0.407 0.523 1 2 - >0.999
ALT升高 27 27 0 >0.999 10 7 0.713 0.398
AST升高 27 29 0.471 0.492 20 15 1.521 0.218
甲状腺功能减退 1 0 - >0.999 0 0 / /
高胆红素血症 12 17 1.538 0.215 0 5 3.462 0.063
白细胞减少症 3 5 0.142 0.706 1 0 - >0.999
血小板减少症 13 12 0.064 0.800 4 2 0.183 0.669
腹痛 25 25 0 >0.999 0 0 / /
腹泻 2 7 2.058 0.151 0 1 - >0.999
发热 6 8 0.091 0.763 0 0 / /
胃出血 1 2 - >0.999 0 0 / /
腹水 6 4 0.471 0.492 0 0 / /
皮疹 0 1 - >0.999 0 0 / /
恶心呕吐 16 12 0.992 0.319 0 0 / /
感觉功能异常 0 2 0.516 0.473 0 0 / /
蛋白尿 0 0 / / 0 0 / /
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