检查点抑制剂在食管癌和胃癌治疗中的作用。

Role of Checkpoint Inhibitors in the Management of Gastroesophageal Cancers.

作者信息

Karim Frederic, Amin Adina, Liu Marie, Vishnuvardhan Nivetha, Amin Saif, Shabbir Raffey, Swed Brandon, Khan Uqba

机构信息

Internal Medicine, New York-Presbyterian Brooklyn Methodist Hospital, 506 6th Street, Brooklyn, NY 11215, USA.

Hematology/Oncology, New York-Presbyterian Brooklyn Methodist Hospital, 506 6th Street, Brooklyn, NY 11215, USA.

出版信息

Cancers (Basel). 2023 Aug 14;15(16):4099. doi: 10.3390/cancers15164099.

DOI:10.3390/cancers15164099

PMID:37627127

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10452271/

Abstract

PURPOSE

This article reviews the essential clinical trials that have led to these immunotherapy approvals and explores the use of predictive biomarkers, such as PD-L1 expression and MSI status, to identify patients who are most likely to benefit from immunotherapies.

METHODS

This case review series describe findings from different clinical trials and contribute to the evolving understanding of the role of CPIs in managing advanced gastroesophageal cancers and may lead to improved treatment options and patient outcomes. Ongoing clinical trials also hold promise for expanding treatment options and improving patient outcomes in the future.

METHODS

The systematic review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol has not been registered. A systematic literature review was conducted to identify relevant clinical trials and studies that describe the role of immune checkpoint inhibitors in managing advanced gastroesophageal cancers. Electronic database (PubMed, Clinicaltrials.gov, Society of Immunotherapy of Cancer, Aliment Pharmacology & Therapeutics, BMC cancer, Molecular Cancer Research, Nature Reviews Molecular Cell Biology, American Association for Cancer Research, Science, Nature, Cancer Discovery, Journal of the National Cancer Institute, Advanced Immunology, Oncotarget, Nature Medicine, Nature Genetics, Gut, Pathology and Oncology Research, Journal of Clinical Oncology, The New England Journal of Medicine, Gastrointestinal oncology, JAMA Oncology, Journal of Gastrointestinal Oncology, Current Oncology, Annals of Oncology, The Lancet, JCO Oncology Practice, Future Oncology, Gastric Cancer, CA: A Cancer Journal for Clinicians, American Journal of Gastroenterology, Gastroenterology, Journal of the National Cancer Institute, International Journal of Epidemiology, Helicobacter, Gastroenterology Review) were searched using a combination of relevant keywords and MESH terms. The search encompassed articles published up to 5/2023. Additionally, manual searches of reference lists of selected articles and pertinent review papers were conducted to ensure comprehensive coverage of relevant studies. Studies were included if they provided insights into clinical trials evaluating the efficacy and safety of CPIs in treating advanced gastroesophageal cancers. Relevant case reviews and trials exploring combination therapies involving CPIs were also considered. Articles discussed in the utilization of predictive biomarkers were included to assess their impact on treatment outcomes. Data from selected studies were extracted to inform the narrative review. Key findings were summarized, including clinical trial designs, patient populations, treatment regimens, response rates, progression-free survival (PFS), overall survival (OS), and adverse events. The role of predictive biomarkers, particularly PD-L1 expression and MSI status, in identifying patients likely to benefit from CPIs was critically evaluated based on study results. Ongoing clinical trials investigating novel combination strategies and exploring the broader scope of CPIs in gastroesophageal cancers were also highlighted. The collected data were synthesized to provide a comprehensive overview of the crucial clinical trials that have contributed to the approval of CPIs for advanced gastroesophageal cancers. The role of CPIs in different lines of therapy, including first-line regimens, was discussed. Furthermore, the evolving landscape of predictive biomarkers was examined, emphasizing their potential significance in optimizing patient selection for CPI therapy. Ongoing clinical trials were reviewed to underscore the continuous efforts in expanding treatment options and improving patient outcomes in the future.

摘要

目的

本文回顾了促成这些免疫疗法获批的关键临床试验，并探讨了使用预测性生物标志物，如程序性死亡配体1（PD-L1）表达和微卫星高度不稳定（MSI）状态，来识别最有可能从免疫疗法中获益的患者。

方法

本病例回顾系列描述了不同临床试验的结果，有助于不断加深对免疫检查点抑制剂（CPI）在晚期胃食管癌治疗中作用的理解，并可能带来更好的治疗选择和患者预后。正在进行的临床试验也有望在未来扩大治疗选择并改善患者预后。

方法

本系统评价遵循系统评价和Meta分析的首选报告项目（PRISMA）的建议。该方案尚未注册。进行了系统的文献检索，以确定描述免疫检查点抑制剂在晚期胃食管癌治疗中作用的相关临床试验和研究。使用相关关键词和医学主题词（MESH）的组合在电子数据库（PubMed、Clinicaltrials.gov、癌症免疫治疗协会、《营养药理学与治疗学》、《BMC癌症》、《分子癌症研究》、《自然评论分子细胞生物学》、美国癌症研究协会、《科学》、《自然》、《癌症发现》、《国家癌症研究所杂志》、《高级免疫学》、《肿瘤靶点》、《自然医学》、《自然遗传学》、《肠道》、《病理学与肿瘤学研究》、《临床肿瘤学杂志》、《新英格兰医学杂志》、胃肠肿瘤学、《美国医学会肿瘤学杂志》、《胃肠肿瘤学杂志》、《当代肿瘤学》、《肿瘤学年鉴》、《柳叶刀》、《JCO肿瘤学实践》、《未来肿瘤学》、《胃癌》、《CA：临床医师癌症杂志》、《美国胃肠病学杂志》、《胃肠病学》、《国家癌症研究所杂志》、《国际流行病学杂志》、《幽门螺杆菌》、《胃肠病学综述》）中进行检索。检索涵盖截至2023年5月发表的文章。此外，还对所选文章和相关综述论文的参考文献列表进行了手工检索，以确保全面涵盖相关研究。如果研究提供了关于评估CPI治疗晚期胃食管癌疗效和安全性的临床试验的见解，则纳入研究。还考虑了探索涉及CPI的联合疗法的相关病例回顾和试验。纳入讨论预测性生物标志物应用的文章，以评估其对治疗结果的影响。提取所选研究的数据以进行叙述性综述。总结了主要发现，包括临床试验设计、患者群体、治疗方案、缓解率、无进展生存期（PFS）、总生存期（OS）和不良事件。根据研究结果，对预测性生物标志物，特别是PD-L1表达和MSI状态，在识别可能从CPI中获益的患者中的作用进行了严格评估。还强调了正在进行的研究新型联合策略以及探索CPI在胃食管癌中更广泛应用范围的临床试验。综合收集的数据，全面概述了促成CPI获批用于晚期胃食管癌的关键临床试验。讨论了CPI在不同治疗线，包括一线治疗方案中的作用。此外，还研究了预测性生物标志物不断变化的格局，强调了它们在优化CPI治疗患者选择方面的潜在重要性。回顾了正在进行的临床试验，以强调未来在扩大治疗选择和改善患者预后方面的持续努力。