Heather Katz1, Layana Biglow2, Mohamed Alsharedi3,4. 1. Department of Hematology/Oncology, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Dr, Huntington, WV, 25701, USA. 2. Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25701, USA. 3. Department of Hematology/Oncology, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Dr, Huntington, WV, 25701, USA. alsharedi@gmail.com. 4. Division of Hematology and Oncology, Joan C. Edwards School of Medicine, Marshall University, Edwards Comprehensive Cancer Center at Cabell Huntington Hospital, 1400 Hal Greer Blvd., Huntington, WV, 25701, USA. alsharedi@gmail.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Katharina Möller; Christoph Fraune; Niclas C Blessin; Maximilian Lennartz; Martina Kluth; Claudia Hube-Magg; Linnea Lindhorst; Roland Dahlem; Margit Fisch; Till Eichenauer; Silke Riechardt; Ronald Simon; Guido Sauter; Franziska Büscheck; Wolfgang Höppner; Cord Matthies; Ousman Doh; Till Krech; Andreas H Marx; Henrik Zecha; Michael Rink; Stefan Steurer; Till S Clauditz Journal: Int Urol Nephrol Date: 2021-04-01 Impact factor: 2.370