接受PD-1抑制剂联合靶向治疗的肝癌人群HBV再激活的临床研究  

Clinical study on HBV reactivation in liver cancer patients receiving PD-1 inhibitor combined with targeted therapy

作　　者：郑唐辉 张真真 陈国彬 张博恒 Zheng Tanghui;Zhang Zhenzhen;Chen Guobin;Zhang Boheng(Department of Hepatic Oncology,Zhongshan Hospital,Fudan University(Xiamen Branch),Xiamen 361009,China;Xiamen Clinical Research Center for Cancer Therapy,Xiamen 361009,China;The Liver Cancer Institute,Fudan University,Shanghai 200032,China;Key Laboratory for Carcinogenesis and Cancer Invasion,The Chinese Ministry of Education,Shanghai 200032,China;Center for Evidence-based Medicine,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院厦门医院肝肿瘤内科,厦门361009 [2]厦门市恶性肿瘤综合治疗临床医学研究中心,厦门361009 [3]复旦大学肝癌研究所,上海200032 [4]癌变与侵袭原理教育部重点实验室,上海200032 [5]复旦大学循证医学中心,上海200032

出　　处：《中国医师杂志》2024年第4期484-488,共5页Journal of Chinese Physician

基　　金：福建省自然科学基金项目(2022J011428);厦门市科技计划指导性项目(3502Z20224ZD1082)。

摘　　要：目的探讨乙型肝炎病毒(HBV)相关性肝癌人群接受程序性死亡受体1(PD-1)抑制剂联合靶向治疗后的HBV再激活发生率,及该治疗中HBV再激活和非再激活人群的预后差别。方法收集2019年1月至2021年6月在复旦大学附属中山医院厦门医院接受PD-1抑制剂联合靶向药物治疗的原发性肝癌患者进行回顾性分析。收集患者年龄、性别、肝功能状态、肝硬化情况、HBV DNA水平、甲胎蛋白、肿瘤分期、抗肿瘤方案及抗HBV方案、肿瘤治疗反应、无进展生存期(PFS)、总生存期(OS)等临床资料进行t检验、χ^(2)检验和Kaplan-Meier生存分析。结果共66例入组患者,其中17例发生HBV再激活,发生率为25.76%;其中3个月、6个月、1年、2年、3年的HBV再激活发生率分别为6.06%(4/66)、12.12%(8/66)、19.70%(13/66)、22.73%(15/66)、25.76%(17/66)。HBV再激活组和非HBV再激活组在年龄、性别、肝功能状态、肝硬化情况、HBV DNA水平、甲胎蛋白、肿瘤分期、抗肿瘤方案及抗HBV方案、客观缓解率(ORR)和疾病控制率(DCR)方面的差异均无统计学意义(均P>0.05)。但HBV再激活组的PFS和OS明显低于非HBV再激活组,分别为4.00个月vs 8.50个月(P=0.002)和12.90个月vs 19.77个月(P=0.014)。结论接受PD-1抑制剂联合靶向治疗的原发性肝癌患者有HBV再激活风险,且发生HBV再激活后的患者肿瘤进展和生存预后明显差于非HBV再激活者。Objective To explore the incidence of hepatitis B virus(HBV)reactivation in the population with HBV associated liver cancer after receiving programmed death receptor 1(PD-1)inhibitors combined with targeted therapy,and the prognostic differences between HBV reactivation and non reactivation populations during this treatment.Methods A retrospective analysis was conducted on patients with primary liver cancer who received PD-1 inhibitor combined with targeted drugs treatment at the Zhongshan Hospital,Fudan University(Xiamen Branch)from January 2019 to June 2021.Clinical data such as age,sex,liver function status,cirrhosis,HBV DNA level,alpha fetoprotein,tumor stage,anti-tumor program and anti HBV program,tumor treatment response,progression free survival(PFS),and total survival(OS)were collected for t test,χ^(2) test and Kaplan-Meier survival analysis.Results A total of 66 enrolled patients were enrolled,of which 17 cases experienced HBV reactivation,with an incidence rate of 25.76%;The rates of HBV reactivation at 3 months,6 months,1 year,2 years,and 3 years were 6.06%(4/66),12.12%(8/66),19.70%(13/66),22.73%(15/66),and 25.76%(17/66),respectively.There was no significant difference between the HBV reactivation group and the non HBV reactivation group in age,sex,liver function status,cirrhosis,HBV DNA level,alpha fetoprotein,tumor stage,anti-tumor and anti HBV programs,objective response rate(ORR)and disease control rate(DCR)(all P>0.05).However,the PFS and OS of the HBV reactivation group were significantly lower than those of the non HBV reactivation group,at 4.00 months vs 8.50 months(P=0.002)and 12.90 months vs 19.77 months(P=0.014),respectively.Conclusions Patients with primary live cancer who receive PD-1 inhibitor combined with targeted therapy are at risk of HBV reactivation,and those who experience HBV reactivation have significantly poorer tumor progression and survival prognosis compared with non HBV reactivated patients.

关 键 词：肝肿瘤 乙型肝炎病毒 免疫检查点抑制剂 靶向治疗 再激活 

分 类 号：R735.7[医药卫生—肿瘤]