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*

doi:10.3969/j.issn.1672-5069.2023.01.029

Abstract

Abstract: Objective The aim of this study was to explore the clinical efficacy of programmed cell death protein-1 (PD-1) inhibitor and lenvatinib in the treatment of elderly patients with advanced primary liver(PLC). Methods 56 patients with advanced PLC were admitted to our hospital between February, 2017 and February, 2020, and were divided into control (n=28) and observation group (n=28), receiving lenvatinib or PD-1 inhibitor, tirelizhu, and lenvatinib combination therapy. The peripheral blood lymphocyte subsets, CD4⁺ cell surface PD-1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) were detected by FCA. Serum acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were detected by ELISA. Results At the end of three month treatment, there were no significant differences as respect to the objective remission rate (42.9% vs. 25.0%) and local control rate(78.6% vs. 64.3%, P>0.05); the percentages of CD3⁺, CD4⁺ and CD8⁺ cells in the combination treatment group were much higher than, while the CD4⁺/CD8⁺ cell ratio, as well as the cell PD-1 and CTLA-4 expression were much lower than in the control (P<0.05); serum aFGF, bFGF and VEGF levels in the observation group were (4.1±0.8)pg/L, (5.1±1.0)pg/L and (13.5±2.7)ng/ml, all significantly lower than [(5.3±0.9)pg/L, (6.1±0.8)pg/L and (18.6±3.1)ng/ml, respectively, P<0.05] in the control; at the end of two-year follow-up, there was no significant difference respect to the progression free survival (10.7% vs. 21.4%, P>0.05) between the two groups, while the overall survival in the observation group was 60.7%, much higher than 25.0% (P<0.05) in the control. Conclusion The strategy of PD-1 inhibitor and lenvatinib combination in the treatment of elderly patients with advanced PLC could improve immune functions and prognosis, which needs further investigation.

Key words: Hepatoma, Programmed cell death protein-1 inhibitor, Lenvatinib, Elderly, Therapy

Peng Yu, Li Haitao, Yang Wenli, et al. Clinical efficacy of PD-1 inhibitor and lenvatinib in the treatment of elderly patients with advanced primary liver cancer[J]. Journal of Practical Hepatology, 2023, 26(1): 112-115.

References

[1] Yang Y, Wang C, Sun H, et al. Apatinib prevents natural killer cell dysfunction to enhance the efficacy of anti-PD-1 immunotherapy in hepatocellular carcinoma. Cancer Gene Ther, 2021, 28(1-2):89-97.
[2] Kim CG, Kim C, Yoon SE, et al. Hyperprogressive disease during PD-1 blockade in patients with advanced hepatocellular carcinoma. J Hepatol, 2021, 74(2):350-359.
[3] Lyu N, Kong Y, Li X, et al. Ablationreboots the response in advanced hepatocellular carcinoma with stable or atypical response during PD-1 therapy: A proof-of-concept study. Front Oncol, 2020, 10(9):580241.
[4] Scheiner B, Kirstein MM, Hucke F, et al. Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort. Aliment Pharmacol Ther, 2019, 49(10):1323-1333.
[5] 中国抗癌协会PLC专业委员会,中华医学会肝病学分会PLC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.
[6] 杨学宁,吴一龙.实体瘤治疗疗效评价标准-RECIST.循证医学,2004,4(2):85-90,111.
[7] 袁冰,张金龙,王茂强,等.TACE后应用仑伐替尼联合PD-1单抗治疗PLC腹膜后淋巴结转移瘤一例.中华转移性肿瘤杂志,2019,2(4):40-41.
[8] 张世同,金建军,白艳丽,等.TACE术后接受恩替卡韦治疗血清HBV DNA阴性的中晚期原发性PLC患者生存率研究.实用肝脏病杂志,2018,21(1):100-103.
[9] 安西全,李燕,孟根才次克.替诺福韦联合索拉非尼治疗乙型肝炎相关中晚期原发性肝癌患者临床观察.实用肝脏病杂志,2021,24(4):600-602.
[10] Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol, 2020, 21(4):571-580.
[11] 袁冰,王燕,张金龙,等.仑伐替尼治疗经肝动脉化疗栓塞术无效的中晚期肝细胞癌患者的临床观察.中华医学杂志,2020,100(11):833-836.
[12] 刘思琪,张秀军,薛源,等.仑伐替尼治疗晚期PLC致单侧间质性肺炎并空洞形成1例.中华肝脏病杂志,2021,29(11):1109-1110.
[13] Sun HC, Zhu XD, Huang C, et al. Initially unresectable hepatocellular carcinoma treated by combination therapy of tyrosine kinase inhibitor and anti-PD-1 antibody followed by resection. J Clin Oncol, 2020, 38(15):e16690-e16690.
[14] 傅云霞,徐梓宁,黄敬君,等.DEB-TACE联合仑伐替尼治疗晚期肝细胞癌的疗效和安全性.中华介入放射学电子杂志,2021,9(2):127-134.
[15] Jiao SC, Bai L, Dong J, et al. Clinical activity and safety of penpulimab (anti-PD-1) with anlotinib as first-line therapy for advanced hepatocellular carcinoma (HCC). J Clin Oncol, 2020, 38(15):4592-4592.
[16] 侯传新,姚光,安磊,等.全身麻醉复合硬膜外麻醉对老年PLC患者心肺功能和术后肺部感染的影响.中华医院感染学杂志,2018,28(9):1377-1379,1383.
[17] 胡亚秋,汪妮,冉锡萍,等.评估免疫检查点抑制剂为基础的联合治疗在原发性肝癌患者中肝损伤发生情况的真实世界研究.中华肝脏病杂志,2022,30(1):57-62.
[18] Chen SC. Fever after anti-programmed cell death-1 treatment to predict the response in advanced hepatocellular carcinoma. J Clin Oncol, 2018, 36(5):90-90.
[19] Bai L, Sun M, Xu A, et al. Phase 2 study of AK104 (PD-1/CTLA-4 bispecific antibody) plus lenvatinib as first-line treatment of unresectable hepatocellular carcinoma. J Clin Oncol, 2021, 39(15):4101-4101.
[20] Li H, Li X, Liu S, et al. PD-1checkpoint blockade in combination with an mTOR inhibitor restrains hepatocellular carcinoma growth induced by hepatoma cell-intrinsic PD-1. Hepatology, 2017, 66(6):1920-1933.
[21] 徐彬,朱小东,黄成,等.仑伐替尼联合程序性死亡受体-1抗体治疗不可切除或进展期肝细胞癌的临床疗效.中华消化外科杂志,2021,20(2):197-204.

Clinical efficacy of PD-1 inhibitor and lenvatinib in the treatment of elderly patients with advanced primary liver cancer

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Shen Yan, Chen Lin. Endoscopic treatment and long-term management of patients with esophagogastric variceal bleeding [J]. Journal of Practical Hepatology, 2023, 26(1): 8-10.
[2]	Zhang Dan, Jiang Jianxin. Comparison of response to recombinant cytokine gene-derived protein or human interferon α-2b and entecavir combination in the treatment of patients with serum HBeAg positive chronic hepatitis B [J]. Journal of Practical Hepatology, 2023, 26(1): 27-30.
[3]	Li Susu, Dong Yuan, Jia Haoyan, et al. Observation of ornithine aspartate at base of colon dialysis in treatment of patients with hepatic encephalopathy [J]. Journal of Practical Hepatology, 2023, 26(1): 75-78.
[4]	Dai Huan, Li Kai, Zhu Yongxiang, et al. Efficacy of endoscopic ligation and tissue glue injection in the treatment of patients with hepatitis B liver cirrhosis and esophageal and gastric varices bleeding [J]. Journal of Practical Hepatology, 2023, 26(1): 87-90.
[5]	Jiang Huizhen, Chen Jun, Chen Chunmei, et al. Performance of quantitative parameters by dynamic contrast-enhanced magnetic resonance imaging in the diagnosis of benign and malignant hepatic space-occupying lesions [J]. Journal of Practical Hepatology, 2023, 26(1): 100-103.
[6]	Gao Xiangrui, Liu Hongyan, Zhang Huai, et al. Differential diagnosis of hepatic hemangioma and hepatocellular carcinoma by multi-b-value diffusion-weighted imaging of high-field magnetic resonance [J]. Journal of Practical Hepatology, 2023, 26(1): 104-107.
[7]	Ding Haibin, Zhang Xin, Li Ya, et al. TACE with sequential microwave ablation followed by oral sorafenib maintenance in treatment of patients with large hepatocellular carcinoma [J]. Journal of Practical Hepatology, 2023, 26(1): 108-111.
[8]	Du Shangyun, Weng Li, Wu Min. Clinical observation of camrelizumab therapy after TACE in the treatment of patients with advanced primary liver cancer [J]. Journal of Practical Hepatology, 2023, 26(1): 116-119.
[9]	Dong Xianjin, Su Wei, Li Liansheng, et al. Comparison of laparoscopic hepatectomy and open hepatectomy in the treatment of patients with intrahepatic cholangiocarcinoma [J]. Journal of Practical Hepatology, 2023, 26(1): 120-123.
[10]	Yin Qiushi, Wang Xueguo, Song Qifeng. Clinical efficacy of laparoscopic hepatectomy in the treatment of patients with intrahepatic bile duct stones [J]. Journal of Practical Hepatology, 2023, 26(1): 124-127.
[11]	Zhang Fu, Chen Junmao, Liang Xiaohui. Efficacy of primary suture laparoscopic common bile duct exploration in the treatment of patients with choledocholithiasis [J]. Journal of Practical Hepatology, 2023, 26(1): 128-131.
[12]	Liu Songhang, Gao Youkui, Cao Liangqi. Clinical efficacy of LC and ERCP in the treatment of patients with gallbladder and extrahepatic bile duct stones [J]. Journal of Practical Hepatology, 2023, 26(1): 132-135.
[13]	Zhang Zixia, Li Delin, Zhang Guoliang. Clinical efficacy of Yipi Yanggan Decoction after radiofrequency ablation in the treatment of patients with primary liver cancer [J]. Journal of Practical Hepatology, 2023, 26(1): 142-144.
[14]	He Xiaojin, Li Dan, Zhou Qing, et al.. Expression of hepatitis B virus X protein and suppressor of cytokine signaling-1 in L02 cells in vitro [J]. Journal of Practical Hepatology, 2022, 25(6): 772-775.
[15]	Li Xiangyang, Ding Guangwei, Jin Ming. Efficacy of entecavir in treatment of patients with chronic hepatitis B and non-alcoholic fatty liver diseases [J]. Journal of Practical Hepatology, 2022, 25(6): 776-779.