实用肿瘤学杂志 ›› 2022, Vol. 36 ›› Issue (6): 489-494.doi: 10.11904/j.issn.1002-3070.2022.06.001

• 消化道肿瘤免疫治疗专题 •    下一篇

免疫治疗联合分子靶向药物治疗中晚期肝细胞癌的临床疗效及安全性分析:一项单臂回顾性研究

王嘉倍, 张运广, 刘连新   

  1. 中国科学技术大学附属第一医院(合肥 230001)
  • 收稿日期:2022-01-10 修回日期:2022-08-10 出版日期:2022-12-28 发布日期:2023-01-06
  • 通讯作者: 刘连新,E-mail:liulx@ustc.edu.cn
  • 作者简介:王嘉倍,男,(1982-),博士,副主任医师,从事肝胆恶性肿瘤治疗的研究
  • 基金资助:
    第五批安徽省“特支计划”创新领军人才(编号:T000525)

Clinical efficacy and safety analysis of immunotherapy combined with molecularly targeted drugs in the treatment of advanced hepatocellular carcinoma:A single-arm retrospective study

WANG Jiabei, ZHANG Yunguang, LIU Lianxin   

  1. The First Affiliated Hospital of University of Science and Technology of China,Hefei 230001,China
  • Received:2022-01-10 Revised:2022-08-10 Online:2022-12-28 Published:2023-01-06

摘要: 目的 探讨免疫治疗联合分子靶向药物治疗中晚期肝细胞癌(HCC)的临床应用价值和安全性。方法 按照入组标准,纳入33例接受免疫治疗联合分子靶向药物治疗的中晚期HCC患者。记录患者用药前的血液生化指标、肿瘤分期、肿瘤影像学特征、既往接受的治疗策略等临床资料,随访患者的影像学复查结果及患者用药过程中发生的不良反应事件,直至随访截止、失访或患者死亡。主要研究终点为客观缓解率(ORR)及安全性,次要研究终点为无进展生存期(PFS)和总生存期(OS)。采用Kaplan-Meier法分析用药患者的临床疗效。结果 截至末次随访,共33例中晚期HCC患者接受了免疫药物与分子靶向药物的联合治疗,ORR为24.2%,疾病控制率(DCR)为66.7%。中位无进展生存期(mPFS)为10.9个月,中位总生存期(mOS)为11.8个月。治疗相关1~2级不良反应事件及发生率分别为恶心呕吐2例(6.1%)、手足皮肤反应2例(6.1%)、反应性皮肤毛细血管增生症2例(6.1%)、乏力1例(3.0%)、胃痛1例(3.0%)、蛋白尿1例(3.0%)、腹痛9例(27.3%)、发热1例(3.0%)、胀气1例(3.0%)、低蛋白血症1例(3.0%)、高胆红素血症5例(15.2%)、谷丙转氨酶升高4例(12.1%)以及谷草转氨酶升高10例(30.3%)。治疗相关3级以上不良反应事件及发生率分别为恶心呕吐1例(3.0%)、腹痛1例(3.0%)和谷草转氨酶升高1例(3.0%)。未观察到与治疗相关死亡事件,不良反应事件均得到有效处理。结论 免疫药物与分子靶向药物的联合使用在中晚期HCC的治疗中,DCR高,不良事件发生率低,可作为中晚期HCC患者一线治疗的选择,值得进一步探索。

关键词: 肝细胞癌, 安全性, 临床疗效, 免疫治疗, 靶向治疗

Abstract: Objective The aim of this study was to explore the clinical application value and safety of immunotherapy combined with molecular targeted drugs in the treatment of advanced hepatocellular carcinoma(HCC).Methods According to the inclusion criteria,33 patients with advanced HCC who received immunotherapy combined with molecular targeted drug therapy were included.The clinical data such as blood biochemical indexes,tumor stage,tumor imaging characteristics and previous treatment strategies of patients before medication were recorded,following up the imaging reexamination results of patients and adverse reactions during medication until the end of follow-up and loss of follow-up or the patient death.The primary endpoints were Objective response rate(ORR)and safety,and the secondary endpoint were progression-free survival(PFS)and overall survival(OS).The Kaplan-Meier method was used to analyze the clinical curative effect of patients taking medication.Results As of the last follow-up,a total of 33 patients with advanced HCC had received the combination therapy of immune drugs and molecular targeted drugs,the ORR and the disease control rate(DCR)were 24.2% and 66.7%,respectively.The median progression-free survival(mPFS)and median overall survival(mOS)were 10.9 months and 11.8 months,respectively.Treatment-related grade 1-2 adverse events and their incidences were nausea and vomiting in 2 cases(6.1%),hand-foot skin reaction in 2 cases(6.1%),reactive cutaneous capillary endothelial proliferation in 2 cases(6.1%),and fatigue in 1 case(3.0%),1 case of stomach pain(3.0%),1 case of proteinuria(3.0%),9 cases of abdominal pain(27.3%),1 case of fever(3.0%),1 case of flatulence(3.0%),hypoalbuminemia 1 case(3.0%),5 cases(15.2%)with hyperbilirubinemia,4 cases with ALT elevation(12.1%),and 10 cases with AST elevation(30.3%).Treatment-related grade 3 or higher adverse reactions and their incidences were nausea and vomiting in 1 case(3.0%),abdominal pain in 1 case(3.0%),and AST elevation in 1 case(3.0%).No treatment-related deaths were observed,and adverse events were all effectively managed.Conclusion The combined use of immune drugs and molecular targeted drugs in the treatment of advanced HCC has a high DCR and a low incidence of adverse events.It can be used as a first-line treatment option for patients with advanced HCC and is worthy of further exploration.

Key words: Hepatocellular carcinoma, Safety, Clinical efficacy, Immunotherapy, Targeted therapy

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