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

摘要/Abstract

摘要： 目的探讨应用程序性细胞死亡蛋白-1(PD-1)抑制剂联合仑伐替尼治疗老年中晚期原发性肝癌(PLC)患者的临床疗效。方法 2017年2月～2020年2月我院收治的56例PLC患者被分为对照组28例和观察组28例,分别给予仑伐替尼治疗或替雷利珠单抗联合仑伐替尼治疗。评估客观缓解率(ORR)和局部控制率(LCR)。使用流式细胞仪检测外周血T淋巴细胞亚群、CD4⁺细胞PD-1和细胞毒性T淋巴细胞相关抗原-4(CTLA-4)表达,采用ELISA法检测血清酸性成纤维细胞生长因子(aFGF)、碱性成纤维细胞生长因子(bFGF)和血管内皮生长因子(VEGF)水平。结果在治疗3月末,两组ORR(42.9%对25.0%)和LCR(78.6% 对64.3%)比较,无显著性差异(P>0.05);观察组CD3⁺、CD4⁺和CD8⁺细胞百分比显著高于对照组,而CD4⁺/CD8⁺细胞比值及细胞PD-1和CTLA-4表达显著低于对照组(P<0.05);观察组血清aFGF、bFGF和VEGF水平分别为(4.1±0.8)pg/L、(5.1±1.0)pg/L和(13.5±2.7)ng/ml,均显著低于对照组【分别为(5.3±0.9)pg/L、(6.1±0.8)pg/L和(18.6±3.1)ng/ml,P<0.05】;在治疗后2年末,两组无进展生存期(PFS)分别为15.0个月和17.9个月,无进展生存率比较无显著性差异(10.7%对21.4%,P>0.05),对照组总体生存期(OS)为18.9个月,观察组为25.7个月,观察组累计生存率显著高于对照组(60.7%对25.0%,P<0.05)。结论应用PD-1抑制剂联合仑伐替尼治疗老年中晚期PLC患者可通过抑制免疫检查点提高机体免疫功能,延长生存期。

关键词: 原发性肝癌, 程序性细胞死亡蛋白-1抑制剂, 仑伐替尼, 老年, 治疗

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

彭雨, 李海涛, 杨文丽, 余意. 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^*[J]. 实用肝脏病杂志, 2023, 26(1): 112-115.

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.

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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^*

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

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