Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.
Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.
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DOI：
10.3390/jcm10122662
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发表时间：
2021-06-16
影响因子：
3.9
通讯作者：
Nielsen DL
中科院分区：
文献类型：
--
作者：
Dyhl-Polk A;Mikkelsen MK;Ladekarl M;Nielsen DL
简介：几种免疫检查点抑制剂（CPI）正在肝细胞癌（HCC）的临床开发中，该领域正在迅速发展。在这篇全面的综述中，我们讨论了已发表的结果并报告了正在进行的临床试验。方法：使用PubMed和EMBASE进行文献检索;还包括国际会议和clinicaltrials.gov上报告的数据。检索于2021年3月5日更新。我们分别评估了CPI单药治疗、CPI联合治疗以及CPI与其他治疗方式联合治疗的研究。仅考虑至少纳入10例患者的研究。结果：我们确定了2649记录发表在英文文献。经过审查，29项研究仍然存在，其中12项研究只有初步数据。在二线背景下的II期研究中，PD-1/PDL-1单药治疗获得的总体缓解率为15-20%，约60%的患者获得疾病控制。在一部分患者中，缓解持续时间较长。此外，安全性特征是可控的。然而，一项比较纳武利单抗与索拉非尼一线治疗的III期研究和一项评估帕博利单抗与二线治疗最佳支持治疗的III期研究并未达到其预定的终点。最近，nivolumab和ipilimumab的I/II期研究在二线治疗中的缓解率约为30%，中位OS为22个月。已经启动了多项试验，以评估CPI与分子靶向药物，特别是抗血管生成药物或局部治疗的组合。一项III期研究调查atezolizumab加贝伐单抗与索拉非尼在一线设置显示显着增加的生存率在组合arm. Conclusions：atezolizumab和贝伐单抗的组合代表了一个新的标准的护理在一线设置为适合患者保留肝功能。CPI可以在晚期HCC患者亚组中产生持久的肿瘤缓解并诱导长期的抗肿瘤免疫。尽管CPI单药治疗的III期试验结果为阴性，但PD-1/PD-L1抑制剂与其他抗血管生成药物、CTLA-4抑制剂或其他方式的联合治疗可能为HCC患者带来新的治疗选择。预测性生物标志物的研究对于进一步开发HCC中的CPI至关重要。
Introduction: Several immune checkpoint inhibitors (CPIs) are under clinical development in hepatocellular carcinoma (HCC) and the field is advancing rapidly. In this comprehensive review, we discuss published results and report on ongoing clinical trials. Methods: A literature search was carried out using PubMed and EMBASE; data reported at international meetings and clinicaltrials.gov were included as well. The search was updated 5 March 2021. We evaluated studies with monotherapy CPI’s, combinations of CPI’s and combinations of CPI’s with other treatment modalities separately. Only studies with at least 10 included patients were considered. Results: We identified 2649 records published in the English language literature. After review, 29 studies remained, including 12 studies with preliminary data only. The obtained overall response rate of PD-1/PDL-1 monotherapy in phase II studies in the second-line setting was 15–20% with disease control in approximately 60% of patients. The responses were of long duration in a subset of patients. Furthermore, the safety profiles were manageable. However, a phase III study comparing nivolumab with sorafenib in the first-line setting and a phase III study evaluating pembrolizumab versus best supportive care in the second-line setting did not meet their prespecified endpoints. More recently, a phase I/II study of nivolumab and ipilimumab has resulted in a response rate of approximately 30% with a median OS of 22 months in the second-line setting. Multiple trials have been initiated to evaluate CPIs in combination with molecularly targeted drugs, especially anti-angiogenic drugs or local therapy. A phase III study investigating atezolizumab plus bevacizumab versus sorafenib in the first-line setting showed significantly increased survival in the combination arm. Conclusions: The combination of atezolizumab and bevacizumab represents a new standard of care in the first-line setting for fit patients with preserved liver function. CPIs can produce durable tumor remission and induce long-standing anti-tumor immunity in a subgroup of patients with advanced HCC. Although phase III trials of CPI monotherapy have been negative, the combination of PD-1/PD-L1 inhibitors with other anti-angiogenic drugs, CTLA-4 inhibitors or other modalities may result in new treatment options for patients with HCC. Research on predictive biomarkers is crucial for further development of CPIs in HCC.
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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
影响因子：
10.9
作者：
Brown ZJ;Heinrich B;Steinberg SM;Yu SJ;Greten TF
通讯作者：
Greten TF
影响因子：
3
作者：
通讯作者：
--
影响因子：
45.3
作者：
Finn, Richard S.;Ikeda, Masafumi;Llovet, Josep M.
通讯作者：
Llovet, Josep M.
影响因子：
3.4
作者：
Chen, Kang-jie;Zhou, Lin;Zheng, Shu-sen
通讯作者：
Zheng, Shu-sen