Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy; Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni, 15 Bologna, Italy.
Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy; Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni, 15 Bologna, Italy.
Cancer Treat Res Commun. 2021;27:100328. doi: 10.1016/j.ctarc.2021.100328. Epub 2021 Feb 2.
Hepatocellular carcinoma (HCC) represents the most commonly diagnosed liver cancer worldwide, and the overall survival of patients with unresectable disease is poor. In the last five years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment scenario of several hematological and solid tumors, and these agents have been actively explored in unresectable HCC. Firstly, promising findings of phase I and II clinical studies reporting durable responses and a tolerable safety profile have led to the assessment of ICIs as single agents in phase III clinical studies; however, the latter have provided controversial results, and the activity of ICI monotherapy seems limited to a small subgroup of patients. Conversely, the IMbrave150 trial recently showed that, among patients with previously untreated unresectable HCC, treatment with atezolizumab plus bevacizumab resulted in significantly longer overall survival and progression-free survival compared to sorafenib monotherapy. In addition, the activity of several other ICIs is under investigation, as combination immunotherapy as well as combinations of immunotherapy with antiangiogenic agents. Nonetheless, there are currently no validated predictive biomarkers able to guide treatment choice in this setting, where the identification of specific predictors of response to ICIs represents a major challenge. In this review, we aim to provide a critical overview of recent evidence on biochemical predictors of response to ICIs in patients with unresectable HCC, especially focusing on PD-L1, TMB, MSI, and other emerging biomarkers.
肝细胞癌 (HCC) 是全球最常见的肝癌，且不可切除疾病患者的总体生存率较差。在过去五年中，免疫检查点抑制剂 (ICI) 彻底改变了多种血液系统和实体瘤的治疗格局，这些药物已在不可切除 HCC 中得到积极探索。首先，具有持久反应和可耐受安全性特征的 I 期和 II 期临床研究的有前景发现促使人们将 ICI 作为单一药物进行 III 期临床研究评估；然而，后者提供了有争议的结果，ICI 单药治疗的活性似乎仅限于一小部分患者。相反，最近的 IMbrave150 试验表明，对于未曾接受过治疗的不可切除 HCC 患者，与索拉非尼单药治疗相比，阿替利珠单抗联合贝伐珠单抗治疗可显著延长总生存期和无进展生存期。此外，其他几种 ICI 的活性正在研究中，包括免疫联合治疗以及免疫联合抗血管生成药物治疗。尽管如此，目前尚无经过验证的预测性生物标志物能够指导这种情况下的治疗选择，而识别对 ICI 有反应的特定预测因子是一个主要挑战。在这篇综述中，我们旨在批判性地综述最近关于不可切除 HCC 患者对 ICI 反应的生化预测因子的证据，特别是重点关注 PD-L1、TMB、MSI 和其他新兴生物标志物。
