Department of Hematology/Oncology, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Dr, Huntington, WV, 25701, USA.
Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25701, USA.
J Gastrointest Cancer. 2020 Jun;51(2):611-619. doi: 10.1007/s12029-019-00243-8.
Upper gastrointestinal (UGI) malignancies including esophageal, gastroesophageal junction (GEJ), and gastric cancers have a poor prognosis in the metastatic setting. Treatment with cytotoxic chemotherapy remains the treatment of choice in the first-line setting with the addition of trastuzumab, a monoclonal antibody against HER-2, if the tumor is HER2-positive. Before the era of checkpoint inhibitors, there were only few treatment options after failure of the first-line systemic therapy.
We extensively searched the English written literature for peer-reviewed manuscripts regarding the use of checkpoint inhibitors in advanced stage and metastatic UGI cancer. We also searched and reviewed ongoing clinical trials from Clinicaltrials.gov.
Checkpoint inhibition is a promising therapeutic option in UGI cancers, which have overexpression of PD-L1, high mutation burden, or microsatellite instability. Checkpoint inhibitors that are being investigated or are approved in advanced UGI malignancies include PD-1 antibodies, nivolumab and pembrolizumab, PD-L1 antibody, avelumab, and CTLA-4 inhibitors, ipilimumab and tremelimumab.
Based on recent and ongoing studies, eligible patients who have progressed beyond the first-line cytotoxic chemotherapy may benefit from immunotherapy. This review outlines the checkpoint inhibitors that are currently or previously being investigated for patients with metastatic UGI cancers.
在上消化道（UGI）恶性肿瘤中，包括食管癌、胃食管交界处（GEJ）癌和胃癌，在转移情况下预后较差。在一线治疗中，细胞毒性化疗仍然是治疗的首选方法，如果肿瘤是 HER2 阳性，则添加曲妥珠单抗（一种针对 HER-2 的单克隆抗体）。在检查点抑制剂时代之前，一线全身治疗失败后仅有少数治疗选择。
我们广泛搜索了英文文献中关于检查点抑制剂在晚期和转移性 UGI 癌症中的使用的同行评审文献。我们还从 Clinicaltrials.gov 搜索并审查了正在进行的临床试验。
在 PD-L1 过表达、高突变负担或微卫星不稳定性的 UGI 癌症中，检查点抑制是一种有前途的治疗选择。正在研究或在晚期 UGI 恶性肿瘤中批准的检查点抑制剂包括 PD-1 抗体、纳武利尤单抗和帕博利珠单抗、PD-L1 抗体阿维鲁单抗和 CTLA-4 抑制剂伊匹单抗和替西木单抗。
基于最近和正在进行的研究，一线细胞毒性化疗后进展的合格患者可能受益于免疫疗法。本综述概述了目前或以前针对转移性 UGI 癌症患者进行研究的检查点抑制剂。
