晚期肝細胞癌的免疫治療：以特殊亞組為重點

StephenW

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Recent advances in clinical practice
Immunotherapy for advanced hepatocellular carcinoma: a focus on special subgroups

    http://orcid.org/0000-0002-7260-532XMatthias Pinter1,2, Bernhard Scheiner1,2, Markus Peck-Radosavljevic3

Author affiliations

    Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria
    Department of Internal Medicine and Gastroenterology (IMuG), Hepatology, Endocrinology, Rheumatology and Nephrology including Centralized Emergency Department (ZAE), Klinikum Klagenfurt am Worthersee, Klagenfurt, Kärnten, Austria

    Correspondence to Dr Matthias Pinter, Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, A-1090, Austria; [email protected]

Abstract

Following the success of immune checkpoint blockers (ICBs) in different cancer types, a large number of studies are currently investigating ICBs in patients with hepatocellular carcinoma (HCC), alone or in combination with other treatments. Both nivolumab and pembrolizumab, as well as the combination of nivolumab plus ipilimumab have been granted accelerated approval by the United States Food and Drug Administration for sorafenib-pretreated patients. While nivolumab and pembrolizumab both failed to meet their primary endpoints in phase III trials, the combination of atezolizumab plus bevacizumab eventually improved overall and progression-free survival compared with sorafenib in a front-line phase III trial, and thus, will become the new standard of care in this setting. Despite this breakthrough, there are patient populations with certain underlying conditions that may not be ideal candidates for this new treatment either due to safety concerns or potential lack of efficacy. In this review, we discuss the safety of ICBs in patients with pre-existing autoimmune disease, IBD or a history of solid organ transplantation. Moreover, we summarise emerging preclinical and clinical data suggesting that ICBs may be less efficacious in patients with underlying non-alcoholic steatohepatitis or HCCs with activated Wnt/β-catenin signalling.
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http://dx.doi.org/10.1136/gutjnl-2020-321702

StephenW

臨床實踐的最新進展
晚期肝細胞癌的免疫治療：以特殊亞組為重點

    http://orcid.org/0000-0002-7260-532XMatthias Pinter1,2，Bernhard Scheiner1,2，Markus Peck-Radosavljevic3

作者單位

    維也納醫科大學內科III消化內科和肝病科，奧地利維也納
    維也納醫科大學維也納肝癌（HCC）研究組，奧地利維也納
    內科與消化內科（IMuG），肝病，內分泌科，風濕病學和腎髒病科，包括中央急診科（ZAE），奧地利克恩根克拉根福市克拉里根福沃根湖畔克拉根福

    對應於維也納醫科大學內科III消化內科和肝病科Matthias Pinter博士，維也納，A-1090，奧地利； [email protected]

抽象

繼免疫檢查點阻滯劑（ICB）在不同類型的癌症中獲得成功之後，目前有大量研究正在單獨或與其他治療聯合研究肝細胞癌（HCC）患者的ICB。美國食品藥品監督管理局已批准了尼古魯單抗和派姆單抗以及尼古魯單抗和依匹莫單抗的聯合治療對索拉非尼預處理的患者進行了加速批准。儘管在第三期臨床試驗中，尼古魯單抗和派姆單抗均未達到其主要終點，但與一線三期臨床試驗中的索拉非尼相比，阿索佐珠單抗和貝伐單抗的聯合最終改善了總體生存率和無進展生存期，因此在這種情況下儘管取得了這一突破，但由於安全性考慮或可能缺乏療效，仍有一些具有某些潛在疾病的患者人群可能不是該新療法的理想候選者。在這篇綜述中，我們討論了ICB在已有自身免疫性疾病，IBD或實體器官移植史的患者中的安全性。此外，我們總結了新興的臨床前和臨床數據，提示ICB在潛在的非酒精性脂肪性肝炎或具有激活的Wnt /β-catenin信號的HCC患者中療效較差。
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http://dx.doi.org/10.1136/gutjnl-2020-321702

StephenW

https://gut.bmj.com/content/earl ... p;utm_term=07082020