阿替利珠单抗联合靶向药物和TACE术治疗中晚期原发性肝癌患者疗效研究*

doi:10.3969/j.issn.1672-5069.2025.05.030

摘要/Abstract

摘要： 目的观察阿替利珠单抗联合靶向药物和肝动脉化疗栓塞(TACE)术治疗中晚期原发性肝癌(PLC)患者的疗效。方法 2017年3月～2021年3月我院收治的中晚期PLC患者126例,被随机分为观察组63例和对照组63例,分别给予TACE术联合磺酸阿帕替尼、或甲苯磺酸索拉菲尼和贝伐珠单抗注射液治疗或在此基础上联合阿替利珠单抗注射液治疗。随访2年,评估客观缓解率(ORR)和疾病控制率(DCR)。使用流式细胞仪检测外周血T淋巴细胞亚群,采用ELISA法检测血清癌胚抗原(CEA)、甲胎蛋白(AFP)和组织多肽抗原(TPA)水平。结果观察组ORR和DCR分别为60.3%和87.3%,均显著高于对照组的41.3%和71.4%(P＜0.05);治疗后,观察组外周血CD4⁺细胞百分比和CD4⁺/CD8⁺细胞比值分别为(38.4±4.3)%和(1.3±0.2),均显著高于对照组【分别为(33.6±3.8)%和(1.1±0.2),P＜0.05】;观察组血清AFP和TPA水平分别为(92.6±25.8)ng/mL和(308.2±50.9)U/L,均显著低于对照组【分别为(177.6±41.3)ng/mL和(359.7±56.3,P＜0.05】;两组2 a生存率分别为66.1%(41/62)和45.0%(27/60),差异显著(x²=5.518,P=0.019)。结论在TACE术后采用阿替利珠单抗联合靶向药物治疗中晚期PLC患者能够提高生存期,可能与改善了免疫功能有关,需要扩大临床验证。

关键词: 原发性肝癌, 阿替利珠, 靶向药物, 经肝动脉化疗栓塞, 治疗, 生存率

Abstract: Objective The aim of this study was to investigate therapeutic efficacy of attilizumab and targeting and immune checkpoint inhibitor (ICPI) combination after transhepatic arterial chemoembolization (TACE) in the treatment of patients with advanced primary liver cancer (aPLC). Methods 126 patients with aPLC were recruited in our hospital between March 2017 and March 2021, and were randomly divided into observation and control group, with 63 cases in each group. TACE was routinely conducted in the two groups, patients in the control group were given apatinib, or sorafenib, and bevaccinium monoantibody therapy, and those in the observation group were treated with attilizumab at base of regimen in the control. All patients were followed-up for two years, and objective response rate (ORR) and disease control rate (DCR) 3 months after treatment were recorded. Peripheral blood T lymphocyte subsets were detected by flow cytometry and serum carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP) and tissue polypeptide antigen (TPA) levels were assayed by ELISA. Results ORR and DCR in the observation group were 60.3% and 87.3%, significantly higher than 41.3% and 71.4% (P<0.05) in the control; after treatment, percentage of peripheral blood CD4⁺ cells and ratio of CD4⁺/CD8⁺ cells in the observation group were (38.4±4.3)% and (1.3±0.2), both significantly higher than [(33.6±3.8)% and (1.1±0.2), respectively, P＜0.05] in the control group; serum AFP and TPA levels were (92.6±25.8)ng/mL and (308.2±50.9)U/L, both much lower than [(177.6±41.3)ng/mL and (359.7±56.3, respectively, P＜0.05] in the control; 2-year survival rate in the observation group was 66.1%(41/62), much higher than 45.0%(27/60, x²=5.518, P=0.019) in the control group. Conclusion Combination of attillizumab, and target and ICPI therapy after TACE in the treatment of patients with aPLC is efficacious, which could prolong survivals, and might be related to the improvement of immune functions.

Key words: Hepatoma, Attilizul, Target medicine, Transhepatic artery chemoembolization, Therapy, Survivals

张小昭, 雷凯, 祁亚斌, 金雷, 朱代华. 阿替利珠单抗联合靶向药物和TACE术治疗中晚期原发性肝癌患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 759-762.

Zhang Xiaozhao, Lei Kai, Qi Yabin, et al. Attilizumab and targeting and immune checkpoint inhibitor combination after TACE in the treatment of patients with advanced primary liver cancer[J]. Journal of Practical Hepatology, 2025, 28(5): 759-762.

参考文献

[1] 姚博文,向俊西,郑鑫,等. 阿替利珠单克隆抗体联合贝伐珠单克隆抗体治疗初始临界可切除中晚期原发性肝癌的临床疗效. 中华消化外科杂志,2022,21(2):303-306.
[2] An J, Han S, Kim HI , et al. Ranking of transarterial and targeted therapies for advanced hepatocellular carcinoma in the era of immuno-oncology: a network meta-analysis of randomized sorafenib-controlled trials. Hepatol Commun, 2022,6(10):2886-2900.
[3] Kim D, Lee JH, Moon H , et al. Development and evaluation of an ultrasound-triggered microbubble combined transarterial chemoembolization (TACE) formulation on rabbit VX2 liver cancer model. Theranostics, 2021,11(1):79-92.
[4] 邱虎,柯少波,蔡高科,等. 免疫检查点抑制剂联合血管内皮生长因子抑制剂一线治疗晚期不可切除肝细胞癌的临床疗效. 中华消化外科杂志,2022,21(S1):29-34.
[5] Ricke J, Schinner R, Seidensticker M , et al. Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma. J Hepatol, 2021,75(6):1387-1396.
[6] Yuan G, Xu Y, Bai X , et al. Autophagy-targeted calcium phosphate nanoparticles enable transarterial chemoembolization for enhanced cancer therapy. ACS Appl Mater Interfaces, 2023 ,15(9):11431-11443.
[7] 中国抗癌协会原发性肝癌专业委员会,中华医学会肝病学分会原发性肝癌学组,中国抗癌协会病理专业委员会,等.原发性肝癌规范化病理诊断指南(2015年版).中华肝脏病杂志,2015,23(5):321-327.
[8] Eisenhauer EA, Therasse P, Bogaerts J , et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer,2009,45(2):228-247.
[9] Liu C, Li T, He JT , et al. TACE combined with microwave ablation therapy vs. TACE alone for treatment of early- and intermediate-stage hepatocellular carcinomas larger than 5 cm: a meta-analysis. Diagn Interv Radiol, 2020,26(6):575-583.
[10] 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 Clin Oncol, 2023,41(1):117-127.
[11] Ghanaati H, Mohammadifard M, Mohammadifard M. A review of applying transarterial chemoembolization (TACE) method for management of hepatocellular carcinoma. J Family Med Prim Care, 2021,10(10):3553-3560.
[12] 黄景铮,蔡明岳,黄文薮,等. 经动脉化疗栓塞联合仑伐替尼及程序性死亡受体1抑制剂治疗不可切除中晚期原发性肝癌的临床疗效分析. 中华放射学杂志,2022,56(8):879-885.
[13] Ye T, Shao SH, Ji K , et al. Evaluation of short-term effects of drug-loaded microspheres and traditional transcatheter arterial chemoembolization in the treatment of advanced liver cancer. World J Gastrointest Oncol, 2022,14(12):2367-2379.
[14] Chiang CL, Chiu KWH, Chan KSK , et al. Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial. Lancet Gastroenterol Hepatol, 2023,8(2):169-178.
[15] Jin J, Zhou T, Lou J , et al. Efficacy of licartin combined with transcatheter hepatic arterial chemoembolization in the treatment of middle-advanced primary liver cancer. J BUON, 2020,25(6):2584-2591.
[16] Xue Y, Gao S, Gou J , et al. Platinum-based chemotherapy in combination with PD-1/PD-L1 inhibitors: preclinical and clinical studies and mechanism of action. Expert Opin Drug Deliv, 2021,18(2):187-203.
[17] Conche C, Finkelmeier F, Pešić M , et al. Combining ferroptosis induction with MDSC blockade renders primary tumours and metastases in liver sensitive to immune checkpoint blockade. Gut, 2023,72(9):1774-1782.
[18] 彭雨,李海涛,杨文丽,等.PD-1抑制剂联合仑伐替尼治疗老年中晚期原发性肝癌患者临床疗效研究.实用肝脏病杂志,2023,26(1):112-115.
[19] Arita J, Ichida A, Nagata R , et al. Conversion surgery after preoperative therapy for advanced hepatocellular carcinoma in the era of molecular targeted therapy and immune checkpoint inhibitors. J Hepatobiliary Pancreat Sci, 2022,29(7):732-740.
[20] El-Khoueiry AB, Sangro B, Yau T , et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet, 2017,389(10088):2492-2502.
[21] Hewitt DB, Rahnemai-Azar AA, Pawlik TM , et al. Potential experimental immune checkpoint inhibitors for the treatment of cancer of the liver. Expert Opin Investig Drugs, 2021,30(8):827-835.
[22] Yuen VW, Chiu DK, Law CT , et al. Using mouse liver cancer models based on somatic genome editing to predict immune checkpoint inhibitor responses. J Hepatol, 2023,78(2):376-389.

阿替利珠单抗联合靶向药物和TACE术治疗中晚期原发性肝癌患者疗效研究^*

Attilizumab and targeting and immune checkpoint inhibitor combination after TACE in the treatment of patients with advanced primary liver cancer

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	中华医学会肝病学分会重型肝病与人工肝学组, 中华医学会肝病学分会终末期肝病营养与再生学组. 慢加急性肝衰竭诊治指南(2025 年版)[J]. 实用肝脏病杂志, 2025, 28(5): 641-647.
[2]	丛东威, 刘丽娜, 高文娟, 黄超群. 干扰素α-2b联合恩替卡韦与干扰素α-2b联合替诺福韦治疗HBeAg阳性慢性乙型肝炎患者疗效比较研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 655-658.
[3]	陈文哲, 王清园, 陈天, 许宇文. ApoB基因多态性对接受聚乙二醇干扰素α治疗的HBeAg阳性慢性乙型肝炎患者疗效的影响^*[J]. 实用肝脏病杂志, 2025, 28(5): 659-662.
[4]	袁铃, 姜霞, 孙美杰, 岳冬黎, 张晓玲. 艾米替诺福韦与丙酚替诺福韦挽救治疗低病毒血症的慢性乙型肝炎患者临床研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 667-670.
[5]	汤勤, 华忠, 苏麒麟, 陈小林. 艾米替诺福韦联合鳖甲煎丸治疗慢性乙型肝炎患者疗效初步研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 671-674.
[6]	郝帅, 王梓依, 张心怡, 张粉娜, 苏娜, 贺娜. 常态化随访实施院内丙型肝炎微消除策略效果评价^*[J]. 实用肝脏病杂志, 2025, 28(5): 675-678.
[7]	刘志东, 李文松, 高震, 孙李妍, 丁琪. 达拉他韦和阿舒瑞韦治疗初治的基因1b型慢性丙型肝炎患者疗效及其外周血淋巴细胞亚群的变化^*[J]. 实用肝脏病杂志, 2025, 28(5): 679-682.
[8]	辛文渊, 李玉薇, 吴君. 达卡他韦联合阿舒瑞韦治疗基因1b型慢性丙型肝炎患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 683-686.
[9]	张磊, 王亚茹, 李会平, 王帅, 张威, 周正, 张帆. 司美格鲁肽治疗2型糖尿病合并非酒精性脂肪性肝炎患者临床初步研究[J]. 实用肝脏病杂志, 2025, 28(5): 699-702.
[10]	王霞, 段旺旺, 李梦辉. 艾塞那肽联合多烯磷脂酰胆碱治疗酒精性肝炎患者初步疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 715-718.
[11]	刘立华, 尤晓红, 范周红. 多烯磷脂酰胆碱联合水飞蓟素治疗102例药物性肝损伤患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 723-726.
[12]	朱颖静, 吴洁, 田鑫越, 田巍巍. 内镜下组织胶注射治疗乙型肝炎肝硬化食管胃底静脉曲张破裂出血患者疗效分析^*[J]. 实用肝脏病杂志, 2025, 28(5): 731-734.
[13]	陈洁, 杨才敏, 彭彩玲, 徐辉. 基于北京PIR分型标准评价恩替卡韦治疗乙型肝炎肝硬化患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 735-738.
[14]	穆亚, 葛乃建, 刘学, 王向东, 徐伟, 杨业发. TACE联合贝伐珠单抗和信迪利单抗治疗不可切除肝细胞癌患者临床疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 751-754.
[15]	徐嘉, 彭炜惟, 尹娜, 杨雨婷. 信迪利单抗联合抗血管内皮生长因子单抗治疗不可手术切除的肝细胞癌患者临床疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 763-766.