肝细胞癌临床试验中的新型免疫治疗组合：它们会塑造未来

StephenW

肝细胞癌临床试验中的新型免疫治疗组合：它们会塑造未来的治疗前景吗？
克劳迪娅·安吉拉·玛丽亚·富尔根齐
, 安东尼奥·达莱西奥
, 奥拉比西·奥贡比伊
, Coskun O. Demirtas
, 亚历山德拉·根纳里
, 阿莱西奥·科尔泰里尼
， 显示所有
2022 年 3 月 18 日接收，2022 年 4 月 28 日接受，在线发布的接受作者版本：2022 年 5 月 4 日

    下载引文 https://doi.org/10.1080/13543784.2022.2072726 CrossMark Logo CrossMark

接受的作者版本
抽象的
介绍

潜在的肝病和内在的化学抗性历来阻碍了 HCC 有效治疗的发展。然而，在过去几年中，基于免疫治疗的组合已成为这种情况下的有效治疗策略。本文批判性地总结了近期HCC全身治疗的治疗进展。
覆盖面积

本文研究了以下 HCC 组合的临床前基本原理：双重检查点抑制剂、免疫检查点抑制剂加抗血管生成剂和免疫检查点抑制剂加酪氨酸激酶抑制剂。介绍了最近的临床研究结果，以及正在进行和未来试验的简要概述。在每个子会议结束时，作者批判性地回顾了当前主要涉及每种方法的安全性和临床适用性的问题。
专家意见

atezolizumab 加贝伐单抗的获批以及 HIMALAYA 试验的积极结果拓宽了晚期 HCC 的治疗方案，同时也为临床医生和研究人员带来了新的挑战。首先，迫切需要用于将患者分配到最佳治疗的预测性生物标志物；迫切需要进行第二项具体研究，以确定新组合在通常被排除在临床试验之外的患者中的使用：例如，肝功能紊乱的患者、HIV 或移植受者。最后，随着新组合被转化为早期阶段，辅助和新辅助设置很快就会发生深刻变化。

关键词：免疫治疗 HCC 全身治疗组合

StephenW

Novel immunotherapy combinations in clinical trials for hepatocellular carcinoma: Will they shape the future treatment landscape?
Claudia Angela Maria Fulgenzi
, Antonio D’Alessio
, Olabisi Ogunbiyi
, Coskun O. Demirtas
, Alessandra Gennari
, Alessio Cortellini
, show all
Received 18 Mar 2022, Accepted 28 Apr 2022, Accepted author version posted online: 04 May 2022

    Download citation https://doi.org/10.1080/13543784.2022.2072726 CrossMark Logo CrossMark

Accepted author version
ABSTRACT
Introduction

Underlying liver disease and the intrinsic chemoresistance have historically hampered the development of efficacious treatments in HCC. However, in the last few years, immunotherapy-based combinations have emerged as efficacious therapeutic strategy in this setting. This paper critically summarises the recent therapeutic progress in the systemic treatment of HCC.
Area covered

This paper examines the preclinical rationale of the following combinations in HCC: dual checkpoint inhibitors, immune checkpoint inhibitors plus anti-angiogenic agents, and immune checkpoint inhibitors plus tyrosine kinase inhibitors. Results of recent clinical studies are presented, along with a brief overview of ongoing and future trials. At the end of each sub session, the authors critically review current issues mainly concerning the safety and clinical applicability of each approach.
Expert opinion

The approval of atezolizumab plus bevacizumab and the positive results of the HIMALAYA trial have broadened the therapeutic scenario for advanced HCC, opening, at the same time, new challenges for clinicians and researchers. First of all, predictive biomarkers to allocate patients to the best treatment are eagerly required; second specific studies are urgently needed to define the use of new combinations in patients usually excluded from clinical trials: e.g., those with deranged liver function, HIV or transplant recipients. Finally, with new combinations being translated into earlier stages, profound changes are soon expected in the adjuvant and neoadjuvant setting.

Keywords: Immunotherapy HCC systemic therapy combinations