免疫检查点抑制剂在晚期肝细胞癌中的实际疗效和安全性：

StephenW

Real-world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: Experience of a tertiary Asian Center
Kennedy Yao Yi Ng  1 , Lawrence Wen Jun Wong  2 , Andrea Jing Shi Ang  2 , Sze Huey Tan  3   4 , Su Pin Choo  1 , David Wai-Meng Tai  1 , Joycelyn Jie Xin Lee  1
Affiliations
Affiliations

    1
    Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
    2
    Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
    3
    Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore.
    4
    Oncology Academic Programme, Duke-NUS Medical School, Singapore.

    PMID: 32875742 DOI: 10.1111/ajco.13454

Abstract

Introduction: Immune checkpoint inhibitor (ICI) use in advanced hepatocellular carcinoma (HCC) is increasing. Real-world data on efficacy and safety, however, are lacking.

Methods: We conducted a retrospective review of all patients with advanced HCC seen at our center who received at least one dose of an ICI between May 2015 and June 2018. Data cutoff was December 31, 2018. Responses were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 criteria.

Results: Of 114 patients, 88.6% were male. Median age was 66 years, 96.5% had an Eastern Cooperative Oncology Group of 0-1. 62.3% received monotherapy ICI. 18.4% of patients had Child-Pugh (CP) B disease on initiation of ICI, and 69.3% had an ALBI grade of 2. 54.4% were known to have chronic hepatitis B (HBV) or were previously infected, and 11.4% had hepatitis C. Baseline HBV viral load (VL) ranged from undetectable to 8 210 000 IU/mL. 35.1% received prior systemic treatment. 28.9% received prior sorafenib. Over a median follow-up duration of 13.8 months (10.4-15.8), ORR was 18.4%, and DCR was 50.9%. Median progression-free survival was 2.7 months (1.3-4.0), and median overall survival (OS) was 13.9 months (6.9-16.2). Thirty-one patients (27.2%) received further systemic therapy after ICI discontinuation. On multivariable analyses, lower albumin level, higher bilirubin level, diuretic-refractory ascites, and HBV-associated HCC were associated with poorer OS. 69.3% of patients experienced adverse events (AE) of any grade, 14.9% of these being grade 3-4. No grade 5 AE were observed. Use of antiviral therapy was associated with a lower risk of grade 3 or above hepatic AEs (P = 0.048), whereas high baseline HBV VL was not associated with an increased risk of reactivation or hepatic AE.

Discussion: We have demonstrated that the real-world performance of ICIs in advanced HCC appears comparable to that observed in clinical trials for HCC patients with CP A cirrhosis. While prognosis of patients with advanced HCC and CP B cirrhosis remains poor even with ICI, usage of ICI is likely to be safe. Patients with HBV with a baseline HBV VL ≥100 IU/mL may receive ICI safely, especially if they are on antiviral treatment.

Keywords: hepatitis B; hepatocellular carcinoma; immune checkpoint inhibitors.

© 2020 John Wiley & Sons Australia, Ltd.

StephenW

免疫检查点抑制剂在晚期肝细胞癌中的实际疗效和安全性：亚洲第三中心的经验
吴坚毅1，劳伦斯·黄文俊2，安德烈·京世昂2，蔡慧敏3 4，苏品C 1，戴伟孟泰1，乔伊斯林·杰辛李1
隶属关系
隶属关系

    1个
    新加坡，新加坡国家癌症中心，医学肿瘤科。
    2
    新加坡国立大学Yong Loo Lin医学院，新加坡。
    3
    新加坡国家癌症中心，临床试验和流行病学系。
    4
    新加坡杜克国大医学院肿瘤学学术课程。

    PMID：32875742 DOI：10.1111 / ajco.13454

抽象

简介：免疫检查点抑制剂（ICI）在晚期肝细胞癌（HCC）中的使用正在增加。但是，缺乏有关功效和安全性的实际数据。

方法：我们对2015年5月至2018年6月间在我中心接受至少一剂ICI的所有晚期HCC患者进行了回顾性研究。数据截止日期为2018年12月31日。肿瘤1.1版标准。

结果：114例患者中，男性占88.6％。中位年龄为66岁，东部合作肿瘤小组为0-1，占96.5％。 62.3％的患者接受了单药ICI治疗。 ICI开始时有18.4％的患者患有Child-Pugh（CP）B病，ALBI等级为2的患者占69.3％，已知患有慢性B型肝炎（HBV）或先前曾感染过，而11.4％的患者患有肝炎C.基线HBV病毒载量（VL）范围从不可检测到8210 000 IU / mL。 35.1％的患者接受了先前的全身治疗。 28.9％的患者接受过索拉非尼治疗。在中位随访时间13.8个月（10.4-15.8）中，ORR为18.4％，DCR为50.9％。中位无进展生存期为2.7个月（1.3-4.0），中位总生存期（OS）为13.9个月（6.9-16.2）。 ICI停用后有31例患者（27.2％）接受了进一步的全身治疗。在多变量分析中，较低的白蛋白水平，较高的胆红素水平，利尿难治性腹水和HBV相关的HCC与较差的OS相关。 69.3％的患者经历任何级别的不良事件（AE），其中14.9％为3-4级。没有观察到5级AE。抗病毒治疗的使用与3级或以上肝AE的风险较低相关（P = 0.048），而高基线HBV VL与再激活或肝AE的风险增加无关。

讨论：我们已经证明，ICI在晚期HCC中的真实表现似乎与在CPA肝硬化的HCC患者的临床试验中观察到的表现相当。尽管即使使用ICI，晚期HCC和CP B肝硬化患者的预后仍然很差，但使用ICI可能是安全的。基线HBV VL≥100IU / mL的HBV患者可以安全接受ICI，特别是在接受抗病毒治疗的情况下。

关键字：乙型肝炎；肝细胞癌；免疫检查点抑制剂。

©2020 John Wiley＆Sons Australia，Ltd.