Hubertus Wald Tumour Centre, University Cancer Centre Hamburg, and Second Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
First Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Mainz, Germany.
Crit Rev Oncol Hematol. 2018 Oct;130:13-26. doi: 10.1016/j.critrevonc.2018.07.001. Epub 2018 Jul 11.
The use of immune checkpoint inhibitors constitutes an emerging therapeutic field for the therapy of gastrointestinal (GI) malignancies following the recent FDA approvals of PD-1 inhibitors for esophago-gastric adenocarcinoma, hepatocellular carcinoma and for microsatellite-instable tumors, which are mainly colorectal cancers. This paper reviews the clinical evidence end of 2017 and discusses the clinical development programs of atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab in GI-tract cancers. Since 2014, these antagonists of the PD-1/PD-L1 axis have gained approval for use in numerous other tumors. Phase II trials and phase I expansion cohorts demonstrate clinical activity in patients with oesophageal, gastric, colorectal, anal and hepatic cancer. Signals of outstanding efficacy are particularly observed in biomarker selected populations and for certain combination regimen. Comprehensive phase III development programs have been initiated in oesophageal and gastric cancer, with randomized trials ongoing in hepatocellular and colorectal cancer as well.
免疫检查点抑制剂的使用构成了胃肠道（GI）恶性肿瘤治疗的一个新兴治疗领域，最近 FDA 批准了 PD-1 抑制剂用于食管胃腺癌、肝细胞癌和微卫星不稳定肿瘤，这些肿瘤主要是结直肠癌。本文综述了 2017 年底的临床证据，并讨论了 atezolizumab、avelumab、durvalumab、nivolumab 和 pembrolizumab 在胃肠道癌症中的临床开发项目。自 2014 年以来，这些 PD-1/PD-L1 轴的拮抗剂已获准用于许多其他肿瘤。II 期试验和 I 期扩展队列显示了这些药物在食管、胃、结直肠、肛门和肝癌患者中的临床活性。在生物标志物选择人群和某些联合方案中观察到了特别显著的疗效信号。在食管癌和胃癌中已经启动了全面的 III 期开发项目，在肝细胞癌和结直肠癌中也正在进行随机试验。
