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Immune Checkpoint Inhibitors in Locally Advanced, Unresectable, and Metastatic Upper Gastrointestinal Malignancies

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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.

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Authors and Affiliations

  1. Department of Hematology/Oncology, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Dr, Huntington, WV, 25701, USA

    Heather Katz & Mohamed Alsharedi

  2. Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25701, USA

    Layana Biglow

  3. 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

    Mohamed Alsharedi

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  1. Heather Katz
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All authors equally contributed to this manuscript.

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Correspondence to Mohamed Alsharedi.

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Katz, H., Biglow, L. & Alsharedi, M. Immune Checkpoint Inhibitors in Locally Advanced, Unresectable, and Metastatic Upper Gastrointestinal Malignancies. J Gastrointest Canc 51, 611–619 (2020). https://doi.org/10.1007/s12029-019-00243-8

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