Shao Yu-Yun, Chen Ching-Tso, Chuang Chien-Huai, Su Tung-Hung, Ho Ming-Chih, Tseng Tai-Chung, Liu Tsung-Hao, Wu Tsung-Che, Cheng Ann-Lii, Hsu Chih-Hung
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
Br J Cancer. 2025 May;132(9):822-827. doi: 10.1038/s41416-025-02978-7. Epub 2025 Mar 24.
Chronic hepatitis B virus (HBV) infection is an etiology of HCC, but clinical trials using immune checkpoint inhibitors (ICIs) usually exclude patients with chronic active hepatitis B (serum HBV viral load > 2000 IU/mL). This study examined the safety and efficacy of concurrently administering the ICI and anti-HBV medications in this patient population.
In this single-arm phase 2 clinical trial, we enrolled patients with advanced HCC and untreated chronic active hepatitis B. Patients received 1500 mg of durvalumab every 4 weeks alone or in combination with 300 mg of tremelimumab on day 1 (the STRIDE regimen). Anti-HBV treatment with entecavir was simultaneously initiated. The primary endpoint was the rate of HBV reactivation.
We enrolled 30 patients, whose mean baseline HBV viral load was 770,986 IU/mL. No patients experienced HBV reactivation or HBV-associated hepatitis. Hepatitis flare was noted in 8 (26.7%) patients, but none of them were associated with HBV reactivation. The objective tumor response rate was 10% and 25% for the durvalumab treatment alone and the STRIDE regimen, respectively.
For patients with chronic active hepatitis B, ICI therapy could be promptly initiated as long as anti-HBV medications were administered simultaneously.
NCT04294498.
慢性乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）的病因之一，但使用免疫检查点抑制剂（ICIs）的临床试验通常会排除慢性活动性乙型肝炎患者（血清HBV病毒载量>2000 IU/mL）。本研究探讨了在该患者群体中同时使用ICIs和抗HBV药物的安全性和有效性。
在这项单臂2期临床试验中，我们纳入了晚期HCC和未经治疗的慢性活动性乙型肝炎患者。患者每4周单独接受1500mg度伐利尤单抗治疗，或在第1天联合300mg曲美木单抗治疗（STRIDE方案）。同时开始使用恩替卡韦进行抗HBV治疗。主要终点是HBV再激活率。
我们纳入了30例患者，其平均基线HBV病毒载量为770,986 IU/mL。没有患者发生HBV再激活或HBV相关肝炎。8例（26.7%）患者出现肝炎发作，但均与HBV再激活无关。度伐利尤单抗单药治疗和STRIDE方案的客观肿瘤缓解率分别为10%和25%。
对于慢性活动性乙型肝炎患者，只要同时给予抗HBV药物，就可以迅速开始ICI治疗。
NCT04294498。
