Lorenzen Sylvie, Lordick Florian, Loosen Sven Heiko, Tacke Frank, Trautwein Christian, Roderburg Christoph, Ettrich Thomas J, Perkhofer Lukas, Reinacher-Schick Anke, Stein Alexander
Department of Hematology and Oncology, Klinikum rechts der Isar, Technical University Munich, Germany.
University Cancer Center, University Clinic Leipzig, Germany.
Z Gastroenterol. 2020 Jun;58(6):542-555. doi: 10.1055/a-1071-8322. Epub 2020 Feb 4.
Gastrointestinal (GI) malignant neoplasms have a high global incidence and a huge impact on cancer-associated mortality. In the past years, excitement was growing among oncologists and patients alike for the use of immunotherapy, specifically immune checkpoint inhibitors. The approval of several PD-1/PD-L1 and CTLA-4 inhibitors radically changed the treatment landscape in many cancer types and established immune-oncology as a new treatment strategy against cancer. Despite major breakthrough reports, shortcomings of immune checkpoint inhibitors (ICI) have been observed, including primary and acquired treatment resistance, especially in patients receiving ICIs as a single treatment. Several immunotherapies for the treatment of GI tumors have recently emerged; however, checkpoint inhibition has not yet shown similar success in GI malignancies compared to other solid tumors. Various phase I-III trials focusing on immunotherapies for GI tumors have found only moderate to unsatisfactory objective response rates (ORR), ranging between 10 % and 25 %. In particular, negative studies have been reported in gastric and pancreatic cancer. Nevertheless, small subsets of cancers, such as DNA mismatch repair deficient (dMMR)/microsatellite instable (MSI) cancers, among others, seem to benefit from treatment with immune checkpoint inhibition. Routine testing for the rare molecular features that can predict response should be implemented in clinical routine for all GI tumors, and large scale clinical trials to identify predictive biomarkers are needed. This article will address the current use and evidence for immunotherapy in GI malignancies and future trends in this area for clinical practice.
胃肠道恶性肿瘤在全球发病率很高，对癌症相关死亡率有巨大影响。在过去几年中，肿瘤学家和患者对免疫疗法，特别是免疫检查点抑制剂的使用越来越感兴趣。几种PD-1/PD-L1和CTLA-4抑制剂的获批从根本上改变了许多癌症类型的治疗格局，并确立了免疫肿瘤学作为一种新的抗癌治疗策略。尽管有重大突破报告，但免疫检查点抑制剂（ICI）的缺点已被观察到，包括原发性和获得性治疗耐药性，特别是在接受ICI单一治疗的患者中。最近出现了几种用于治疗胃肠道肿瘤的免疫疗法；然而，与其他实体瘤相比，检查点抑制在胃肠道恶性肿瘤中尚未显示出类似的成功。各种针对胃肠道肿瘤免疫疗法的I-III期试验仅发现客观缓解率（ORR）为中等至不理想，在10%至25%之间。特别是，在胃癌和胰腺癌中已有阴性研究报告。然而，一小部分癌症，如DNA错配修复缺陷（dMMR）/微卫星不稳定（MSI）癌症等，似乎从免疫检查点抑制治疗中受益。对于所有胃肠道肿瘤，应在临床常规中对可预测反应的罕见分子特征进行常规检测，并且需要进行大规模临床试验以确定预测性生物标志物。本文将探讨免疫疗法在胃肠道恶性肿瘤中的当前应用和证据以及该领域临床实践的未来趋势。
