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2020年更新:免疫检查点抑制剂治疗转移性结直肠癌的现状

Current Treatments of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitors-2020 Update.

作者信息

Jung Gerhard, Benítez-Ribas Daniel, Sánchez Ariadna, Balaguer Francesc

机构信息

Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, 08036 Barcelona, Spain.

Colorectal Cancer Research Laboratory, Institute for Research in Biomedicine, Parc Científic de Barcelona, 08028 Barcelona, Spain.

出版信息

J Clin Med. 2020 Oct 31;9(11):3520. doi: 10.3390/jcm9113520.

Abstract

During the last 20 years, chemotherapy has improved survival rates of colorectal cancer (CRC). However, the majority of metastatic cases do not respond to or progress after first line conventional chemotherapy and contribute to the fatalities of patients with CRC. Insights into the immune contexture of the tumor microenvironment (TME) have enabled the development of new systemic treatments that boost the host immune system against the tumor-the immune checkpoint inhibitors (ICI). These promising drugs have already shown astonishing efficacies in other cancer types and have raised new hope for the treatment of metastatic CRC (mCRC). In this review, we will summarize the results of the clinical trials that led to their accelerated approval by the U.S. Food and Drug Administration (FDA) in 2017, as well as all relevant recent studies conducted since then-some of which are not published yet. We will focus on therapeutic efficacy, but also discuss the available data for drug safety and security, changes in quality of life indicators and predictive biomarkers for treatment response. The burgeoning evidence for a potential use of ICIs in other settings than mCRC will also be mentioned. For each trial, we have made a preliminary assessment of the quality of clinical trial design and of the "European Society of Medical Oncology (ESMO) magnitude of clinical benefit" (ESMO-MCBS) in order to provide the first evidence-based recommendation to the reader.

摘要

在过去20年里,化疗提高了结直肠癌(CRC)的生存率。然而,大多数转移性病例对一线传统化疗无反应或在化疗后病情进展,这导致了CRC患者的死亡。对肿瘤微环境(TME)免疫背景的深入了解促使了新的全身治疗方法的发展,即增强宿主免疫系统对抗肿瘤的免疫检查点抑制剂(ICI)。这些有前景的药物已在其他癌症类型中显示出惊人的疗效,并为转移性结直肠癌(mCRC)的治疗带来了新希望。在这篇综述中,我们将总结那些促使其于2017年被美国食品药品监督管理局(FDA)加速批准的临床试验结果,以及此后进行的所有相关最新研究——其中一些研究尚未发表。我们将重点关注治疗效果,同时也会讨论药物安全性和保障性的现有数据、生活质量指标的变化以及治疗反应的预测生物标志物。还将提及ICI在mCRC以外的其他情况下潜在应用的新出现证据。对于每项试验,我们对临床试验设计质量和“欧洲医学肿瘤学会(ESMO)临床获益程度”(ESMO-MCBS)进行了初步评估,以便为读者提供首个基于证据的建议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/7694085/df22276772e9/jcm-09-03520-g001.jpg

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