Atezolizumab-bevacizumab plus Y-90 TARE for the treatment of hepatocellular carcinoma: preclinical rationale and ongoing clinical trials
Atezolizumab-bevacizumab plus Y-90 TARE for the treatment of hepatocellular carcinoma: preclinical rationale and ongoing clinical trials
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DOI：
10.1080/13543784.2022.2009455
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发表时间：
2021-12-03
影响因子：
6.1
通讯作者：
Brandi, Giovanni
中科院分区：
文献类型：
--
作者：
Di Federico, Alessandro;Rizzo, Alessandro;Brandi, Giovanni
简介 自免疫疗法引入以来，晚期肝细胞癌 (HCC) 的治疗方案不断发展。 IMbrave150 试验将 atezolizumab-bevacizumab 设置为不可切除 HCC 患者的新标准一线治疗。然而，对于中晚期门静脉血栓形成但无远处转移的患者，(90)钇经动脉放射栓塞术(Y-90-TARE)被认为是首选治疗方法。涵盖领域 我们讨论了有关 Y-90-TARE 在 HCC 中使用的主要证据、该肿瘤免疫治疗的最新进展，以及 VEGF 阻断与其他两种治疗策略相结合的临床前基本原理。专家观点 HCC具有极其异质的肿瘤免疫微环境。这可能解释了免疫检查点抑制剂获得的不一致结果的原因。确定最能从免疫治疗中受益的患者至关重要；然而，缺乏可靠的反应标志。放射治疗和 VEGF 抑制与免疫治疗具有明确的协同作用，主要与增强抗原呈递和减少免疫抑制性免疫浸润有关。因此，将免疫检查点抑制剂与 VEGF 阻断和 Y-90-TARE 相结合可能会克服单独使用这些治疗方法时观察到的主要耐药性。
Introduction The treatment algorithm of advanced hepatocellular carcinoma (HCC) has evolved since the introduction of immunotherapy. The IMbrave150 trial set atezolizumab-bevacizumab as a new standard-of-care first-line treatment for unresectable HCC patients. However, for patients with intermediate or advanced stage with portal vein thrombosis but without distant metastases, (90)Yttrium transarterial radioembolization (Y-90-TARE) is considered the treatment of choice. Areas Covered We discuss the main evidence regarding the use of Y-90-TARE in HCC, the recent progress of immunotherapy in this tumor, and the preclinical rationale of combining VEGF blockade with the other two treatment strategies. Expert opinion HCC has an extremely heterogeneous tumor immune microenvironment. This may explain the inconsistent outcomes obtained with immune-checkpoint inhibitors. The identification of patients who could benefit most from immunotherapy is crucial; however, reliable markers of response are lacking. Radiation therapy and VEGF inhibition have an established synergism with immunotherapy, mainly linked to enhanced antigen presentation and reduced immunosuppressive immune infiltrate. Combining an immune-checkpoint inhibitor with VEGF blockade and Y-90-TARE might hence overcome primary resistances observed when each of these treatments is administerd alone.