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食管癌和胃癌免疫治疗的现状与未来展望

Current and Future Aspects of Immunotherapy for Esophageal and Gastric Malignancies.

作者信息

De Mello Ramon Andrade, Lordick Florian, Muro Kei, Janjigian Yelena Y

机构信息

1 Algarve Biomedical Centre/Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.

2 Division of Medical Oncology, School of Medicine, Nove de Julho University, Bauru Campus, São Paulo, Brazil.

出版信息

Am Soc Clin Oncol Educ Book. 2019 Jan;39:237-247. doi: 10.1200/EDBK_236699. Epub 2019 May 17.

Abstract

Esophagogastric (EG) cancer has a poor prognosis despite the use of standard therapies, such as chemotherapy and biologic agents. Recently, immune checkpoint inhibitors (ICIs) have been introduced as treatments for EG cancer; nivolumab and pembrolizumab have been approved in the United States and Europe to treat advanced EG cancer. Other ICIs, such as avelumab, durvalumab, ipilimumab, and tremelimumab, have been evaluated in several trials, although their roles are still not established in clinical practice. In addition, preclinical evidence suggests that combining an ICI with a tumor-targeting antibody can result in greater antitumor effects in metastatic EG cancer. There are not yet validated predictive biomarkers to identify which patients will respond best to ICI treatment. PD-L1 expression may predict intensity of response, although PD-L1-negative patients can still respond to ICIs. Despite differences in PD-L1 expression between Asian and non-Asian populations, no geographic differences in rates of treatment-related or immune-mediated/infusion-related adverse events have been reported. Also, several trials are currently evaluating combinations of ICIs, standard chemotherapy, and biologic agents as well as novel biomarkers to improve treatments and outcomes. Our review will address the current use of and evidence for ICIs for advanced EG cancer treatment and future trends in this area for clinical practice.

摘要

尽管使用了化疗和生物制剂等标准疗法,但食管胃癌(EG)的预后仍然很差。最近,免疫检查点抑制剂(ICI)已被引入作为EG癌的治疗方法;纳武单抗和派姆单抗已在美国和欧洲被批准用于治疗晚期EG癌。其他ICI,如阿维鲁单抗、度伐鲁单抗、伊匹单抗和曲美木单抗,已在多项试验中进行了评估,尽管它们在临床实践中的作用仍未确立。此外,临床前证据表明,将ICI与肿瘤靶向抗体联合使用可在转移性EG癌中产生更大的抗肿瘤效果。目前还没有经过验证的预测生物标志物来确定哪些患者对ICI治疗反应最佳。PD-L1表达可能预测反应强度,尽管PD-L1阴性患者仍可对ICI产生反应。尽管亚洲和非亚洲人群的PD-L1表达存在差异,但尚未报道治疗相关或免疫介导/输液相关不良事件发生率的地理差异。此外,目前有几项试验正在评估ICI、标准化疗和生物制剂的联合使用以及新型生物标志物,以改善治疗效果和预后。我们的综述将探讨ICI在晚期EG癌治疗中的当前应用和证据,以及该领域临床实践的未来趋势。

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