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.
目的：本文综述了促成这些免疫疗法获批的关键临床试验，并探讨了利用PD-L1表达和MSI状态等预测性生物标志物来识别最可能从免疫疗法中获益的患者。方法：本病例综述系列描述了不同临床试验的发现，有助于深化对免疫检查点抑制剂在晚期胃食管癌治疗中作用的理解，并可能推动治疗方案和患者预后的改善。正在进行的临床试验也为未来拓展治疗选择和改善患者预后带来希望。方法：本系统综述遵循《系统综述和荟萃分析优先报告条目》的建议。研究方案未进行注册。通过系统性文献检索，识别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组合检索了电子数据库（包括PubMed、Clinicaltrials.gov、癌症免疫治疗学会、Aliment Pharmacology & Therapeutics、BMC癌症、分子癌症研究、Nature Reviews分子细胞生物学、美国癌症研究协会、Science、Nature、Cancer Discovery、美国国家癌症研究所杂志、Advanced Immunology、Oncotarget、Nature Medicine、Nature Genetics、Gut、病理学与肿瘤学研究、临床肿瘤学杂志、新英格兰医学杂志、胃肠道肿瘤学、JAMA Oncology、胃肠道肿瘤学杂志、Current Oncology、肿瘤学年鉴、柳叶刀、JCO肿瘤学实践、Future Oncology、胃癌、CA: 临床医师癌症杂志、美国胃肠病学杂志、胃肠病学、美国国家癌症研究所杂志、国际流行病学杂志、Helicobacter、胃肠病学评论）。检索涵盖截至2023年5月发表的文章。此外，对选定文章和相关综述论文的参考文献列表进行了人工检索，以确保全面覆盖相关研究。纳入标准为：提供关于评估免疫检查点抑制剂治疗晚期胃食管癌疗效和安全性的临床试验见解的研究。也考虑了涉及免疫检查点抑制剂的联合疗法的相关病例综述和试验。纳入讨论了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。提取选定研究的数据以形成叙述性综述。总结了关键发现，包括临床试验设计、患者人群、治疗方案、缓解率、无进展生存期、总生存期和不良事件。根据研究结果，批判性评估了预测性生物标志物（特别是PD-L1表达和MSI状态）在识别可能从免疫检查点抑制剂中获益的患者方面的作用。同时强调了正在进行的、研究新型联合策略及探索免疫检查点抑制剂在胃食管癌中更广泛应用范围的临床试验。综合所收集的数据，全面概述了促成免疫检查点抑制剂获批用于晚期胃食管癌治疗的关键临床试验。讨论了免疫检查点抑制剂在不同治疗线（包括一线方案）中的作用。此外，审视了预测性生物标志物不断发展的格局，强调了其在优化免疫检查点抑制剂治疗患者选择方面的潜在意义。回顾了正在进行的临床试验，以强调未来在拓展治疗选择和改善患者预后方面持续不断的努力。
Role of Checkpoint Inhibitors in the Management of Gastroesophageal Cancers
肿瘤(癌症)患者之家