首页|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

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

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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、x2x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 fetoprotcin,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,x2 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 Patientswith 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.

Liver neoplasmsHepatitis B virusImmune checkpoint inhibitorsTargeted therapyReactivation

郑唐辉、张真真、陈国彬、张博恒

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复旦大学附属中山医院厦门医院肝肿瘤内科,厦门 361009

厦门市恶性肿瘤综合治疗临床医学研究中心,厦门 361009

复旦大学肝癌研究所,上海 200032

癌变与侵袭原理教育部重点实验室,上海 200032

复旦大学循证医学中心,上海 200032

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肝肿瘤 乙型肝炎病毒 免疫检查点抑制剂 靶向治疗 再激活

福建省自然科学基金厦门市科技计划指导性项目

2022J0114283502Z20224ZD1082

2024

中国医师杂志
中华医学会 湖南省医学会

中国医师杂志

CSTPCD
影响因子:0.876
ISSN:1008-1372
年,卷(期):2024.26(4)
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