Clinical efficacy of donafenib combined with PD-1 inhibitor and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma

SU Lan; ZHU Jinghan; LIU Mingming; YANG Yarong; ZHANG Yu; CHEN Zutao

doi:10.6039/j.issn.1001-0408.2025.21.13

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Clinical efficacy of donafenib combined with PD-1 inhibitor and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma

更新时间：2025-11-10

- Clinical efficacy of donafenib combined with PD-1 inhibitor and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma
- ZHONGGUO YAOFANG Vol. 36, Issue 21, Pages: 2692-2698(2025)
- 作者机构：
  
  1.苏州大学附属第四医院感染与肝病科，江苏苏州　215000
  2.苏州大学附属第一医院感染科，江苏苏州　215006
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.21.13
  CLC： R969.4;R735.7;R979.1
- Received：10 July 2025，
  
  Revised：2025-10-16，
  
  Accepted：16 October 2025，
  
  Published：15 November 2025
- 稿件说明：
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苏兰,朱婧菡,刘明明,等.多纳非尼联合PD-1抑制剂及血管介入治疗在不可切除肝细胞癌中的临床效果观察[J].中国药房,2025,36(21):2692-2698.

SU Lan,ZHU Jinghan,LIU Mingming,et al.Clinical efficacy of donafenib combined with PD-1 inhibitor and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma[J].ZHONGGUO YAOFANG,2025,36(21):2692-2698.
苏兰,朱婧菡,刘明明,等.多纳非尼联合PD-1抑制剂及血管介入治疗在不可切除肝细胞癌中的临床效果观察[J].中国药房,2025,36(21):2692-2698. DOI： 10.6039/j.issn.1001-0408.2025.21.13.

SU Lan,ZHU Jinghan,LIU Mingming,et al.Clinical efficacy of donafenib combined with PD-1 inhibitor and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma[J].ZHONGGUO YAOFANG,2025,36(21):2692-2698. DOI： 10.6039/j.issn.1001-0408.2025.21.13.

摘要

目的

观察多纳非尼联合程序性死亡受体1（PD-1）抑制剂及血管介入治疗在不可切除肝细胞癌（HCC）中的临床效果。

方法

回顾性选取2022年6月至2023年3月苏州大学附属第四医院和苏州大学附属第一医院接受PD-1抑制剂（替雷利珠单抗或者信迪利单抗，下同）联合血管介入治疗（对照组，89例）和多纳非尼联合PD-1抑制剂及血管介入治疗（观察组，76例）共计165例不可切除HCC患者的临床资料。比较两组患者的近期疗效（治疗后3个月）、远期疗效（治疗后2年），治疗前和治疗3个月后的肝功能指标（血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素）和肿瘤标志物（血清甲胎蛋白、癌胚抗原、糖类抗原19-9、异常凝血酶原）水平，以及治疗期间的药物不良反应（ADR）发生情况；并对总有效率（ORR）进行基于PD-1抑制剂种类的亚组分析。

结果

治疗后，观察组患者的ORR显著高于对照组（

＜0.05），疾病控制率虽然高于对照组但差异无统计学意义（

＞0.05）。观察组患者的中位总生存期为16.9个月[95%置信区间（CI）为14.2～19.1个月

]

，显著长于对照组（12.4个月，95%CI为10.1～15.3个月）（

＜0.05）。亚组分析结果显示，该疗效优势在信迪利单抗亚组与替雷利珠单抗亚组中的趋势一致，且亚组间无显著异质性（

＞0.1，

＜0.001%）。治疗前，两组患者的上述肝功能指标和肿瘤标志物水平比较，差异均无统计学意义（

＞0.05）；治疗后，两组患者的肝功能指标和肿瘤标志物水平均较治疗前显著降低（

＜0.05），且观察组降低得更明显（

＜0.05）。两组患者的ADR总发生率和3级及以上ADR的发生率比较，差异均无统计学意义（

＞0.05）。

结论

对于不可切除的HCC患者，多纳非尼联合PD-1抑制剂及血管介入治疗有望能获得较好的临床疗效，且不增加治疗相关的ADR风险。

Abstract

OBJECTIVE

To observe the clinical efficacy of donafenib combined with programmed death-1 （PD-1） inhibitors and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma （HCC）.

METHODS

This retrospective study included 165 patients with unresectable HCC who were treated at the Fourth and First Affiliated Hospitals of Soochow University between June 2022 and March 2023. Among them， 89 patients received PD-1 inhibitors （tislelizumab or sintilimab， similarly hereinafter） plus vascular intervention （control group） and 76 patients received donafenib in combination with PD-1 inhibitors and vascular intervention （observation group）. Short-term efficacy （3 months after treatment）， long-term efficacy （2 years after treatment）， the levels of liver function indexes [serum alanine amino-transferase （ALT）， aspartate transferase （AST）， and total bilirubin （TBil）] and tumor biomarkers [alpha fetoprotein （AFP）， carcinoembryonic antigen （CEA）， carbohydrate antigen 19-9 （CA19-9）， and des-gamma-carboxy prothrombin （DCP）] before treatment and after 3 months of treatment， as well as the occurrence of adverse drug reaction （ADR） during treatment， were compared between the two groups. In addition， overall response rate （ORR） stratified by PD-1 inhibitor type was analyzed.

RESULTS

After treatment， the ORR was significantly higher in the observation group than in the control group （

＜0.05）； although the disease control rate was higher in the observation group compared to the control group， the difference was not statistically significant （

＞0.05）. The median overall survival of patients in the observation group was 16.9 months [95% confidence interval （CI）： 14.2 to 19.1 months

]

， which was significantly longer than that in the control group （12.4 months， 95%CI： 10.1 to 15.3 months）（

＜0.05）. Subgroup analysis result indicated that therapeutic advantage was consistent across both sintilimab and tislelizumab subgroups， with no significant heterogeneity （

＞0.1，

＜0.001%）. Before treatment， there were no significant differences in liver function indexes or tumor marker levels between 2 groups （

＞0.05）. After treatment， both groups showed significant declines in these indicators compared with baseline （

＜0.05）， with greater reductions observed in the observation group （

＜0.05）. There were no statistically significant differences in overall incidence of ADR and grade ≥3 ADRs between the two groups （

＞0.05）.

CONCLUSIONS

For patients with unresectable HCC， the combination of donafenib， PD-1 inhibitors and vascular intervention therapy may achieve superior clinical outcomes without increasing the risk of treatment-related ADR.

关键词

Keywords

references

BI X Y ， ZHAO H T ， ZHAO H ， et al . Consensus of Chinese experts on neoadjuvant and conversion therapies for hepatocellular carcinoma：2023 update [J ] . Liver Cancer ， 2025 ， 14 （ 2 ）： 223 - 238 .

胡晓云，臧梦雅，李祺，等 . 阿替利珠单克隆抗体联合贝伐珠单克隆抗体一线治疗不可切除肝细胞癌的临床疗效 [J ] . 中华消化外科杂志， 2021 （增刊2 ）： 20 - 24 .

WANG G L ， ZHANG J X ， LIU H ， et al . Embolization alone is as effective as TACE for unresectable HCC：systematic review and meta-analysis of randomized controlled trials [J ] . BMC Gastroenterol ， 2024 ， 24 （ 1 ）： 195 .

LANZA C ， ASCENTI V ， AMATO G V ， et al . All you need to know about TACE：a comprehensive review of indications，techniques，efficacy，limits，and technical advancement [J ] . J Clin Med ， 2025 ， 14 （ 2 ）： 314 .

DING Z R ， FANG G X ， TANG Y Y ， et al . The impact of PD-1 inhibitors on prognosis in unresectable hepatocellular carcinoma treated with TACE and lenvatinib：a retrospective study [J ] . Sci Rep ， 2024 ， 14 （ 1 ）： 14334 .

LI J P ， LI Y ， SONG J L ， et al . Efficacy and safety analysis of transarterial chemoembolization plus donafenib with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma：a prospective，single-arm，single-center，phase Ⅱ clinical study [J ] . J Hepatocell Carcinoma ， 2024 ， 11 ： 1207 - 1219 .

国家卫生健康委办公厅 . 原发性肝癌诊疗指南：2022年版 [J ] . 临床肝胆病杂志， 2022 ， 38 （ 2 ）： 288 - 303 .

LLOVET J M ， ZUCMAN-ROSSI J ， PIKARSKY E ， et al . Hepatocellular carcinoma [J ] . Nat Rev Dis Primers ， 2016 ， 2 ： 16018 .

GORDAN J D ， KENNEDY E B ， ABOU-ALFA G K ， et al . Systemic therapy for advanced hepatocellular carcinoma：ASCO guideline update [J ] . J Clin Oncol ， 2024 ， 42 （ 15 ）： 1830 - 1850 .

LEE J ， JIN Y J ， SHIN S K ， et al . Clinical outcomes of transarterial chemoembolization in Child-Turcotte Pugh class A patients with a single small （≤3 cm） hepatocellular carcinoma [J ] . J Gastroenterol Hepatol ， 2024 ， 39 （ 9 ）： 1924 - 1931 .

KIM D H ， MIN E J ， KIM B ， et al . RECIST 1.1， mRECIST，and Choi criteria for evaluating treatment response and survival outcomes in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab [J ] . Eur Radiol ， 2025 ， 35 （ 2 ）： 684 - 694 .

National Cancer Institute . Common terminology criteria for adverse events （CTCAE） version 5 [EB/OL ] . [ 2025-09-21 ] . https：//ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm .

LOU Y D ， ZHANG X L ， SUN P F ， et al . Hepatic arterial infusion chemotherapy enhances the efficacy of lenvatinib plus PD-1 inhibitors in hepatocellular carcinoma patients with tumor thrombosis in the inferior vena cava and/or right atrium [J ] . Acad Radiol ， 2025 ， 32 （ 2 ）： 787 - 797 .

WANG M X ， LAI T ， LIU A X ， et al . Comparative efficacy of transarterial chemoembolization with and without PD-1 inhibitor in the treatment of unresectable liver cancer and construction and validation of prognostic models [J ] . Transl Cancer Res ， 2025 ， 14 （ 1 ）： 383 - 403 .

JIANG J Y ， ZHANG H ， OU Y J ， et al . The immune-reinforcements of lenvatinib plus anti-PD-1 and their rationale to unite with TACE for unresectable hepatocellular carcinoma treatment [J ] . Immunol Lett ， 2025 ， 275 ： 107003 .

MA Y H ， SUN Y G ， AILIKENJIANG K ， et al . Donafenib induces mitochondrial dysfunction in liver cancer cells via DRP1 [J ] . Cell Biochem Biophys ， 2025 ， 83 （ 2 ）： 2379 - 2388 .

DENG W ， XIE J ， WANG T ， et al . The safety and efficacy of tyrosine kinase inhibitors and programmed cell death protein-1 inhibitors combined with HAIC/TACE in the treatment of recurrent unresectable hepatocellular carcinoma [J ] . BMC Cancer ， 2025 ， 25 （ 1 ）： 779 .

LI H ， DAI Y F ， WU D ， et al . Integrated multi-omics de- monstrates enhanced antitumor efficacy of donafenib combined with FADS2 inhibition in hepatocellular carcinoma [J ] . Transl Oncol ， 2025 ， 51 ： 102142 .

叶禾清，李杰，张玉元，等 . 载药微球化疗栓塞联合多纳非尼及PD-1治疗中晚期大肝癌的疗效分析 [J/OL ] . 中华介入放射学电子杂志， 2024 ， 12 （ 3 ）： 212 - 216 [ 2025-03-04 ] . https：//zhjrfsxdzzz.cma-cmc.com.cn/CN/10.3877/cma.j.issn.2095-5782.2024.03.004 https://zhjrfsxdzzz.cma-cmc.com.cn/CN/10.3877/cma.j.issn.2095-5782.2024.03.004 .

DENG L W ， SUN Y Y ， WANG H Q ， et al . Efficacy and safety of transarterial chemoembolization plus donafenib with or without immune checkpoint inhibitors as the first-line treatment for unresectable hepatocellular carcinoma：a propensity score matching analysis [J ] . J Hepatocell Carcinoma ， 2024 ， 11 ： 29 - 38 .

王宏博，刘福晨，刘辉，等 . 经肝动脉化疗栓塞术联合多纳非尼与替雷利珠单抗治疗中晚期肝癌34例 [J ] . 临床放射学杂志， 2024 ， 43 （ 3 ）： 443 - 449 .

郭泽毅，伍焱平，谢庆余，等 . 中晚期肝癌多纳非尼联合抗PD-1单抗、HAIC治疗成功转化1例 [J ] . 临床肿瘤学杂志， 2022 ， 27 （ 7 ）： 669 - 670 .

XIAO X H ， FU H X ， QIN H X ， et al . Case report：complete response after transcatheter arterial chemoembolization combined with donafenib plus tislelizumab therapy for hepatocellular carcinoma with main trunk portal vein tumor thrombus in a patient coinfected with HIV and HBV [J ] . Front Immunol ， 2024 ， 15 ： 1422801 .

WANG J T ， LI J ， TANG G J ， et al . Clinical outcomes and influencing factors of PD-1/PD-L1 in hepatocellular carcinoma [J ] . Oncol Lett ， 2021 ， 21 （ 4 ）： 279 .

张伟，高炜，刘晨，等 . 多纳非尼联合HAIC和信迪利单抗治疗伴下腔静脉癌栓的肝细胞癌并完全缓解一例 [J ] . 天津医药， 2023 ， 51 （ 2 ）： 203 - 206 .

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