Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence
To date, several trials have evaluated the safety and efficacy of immune-checkpoint inhibitors (ICI) for the treatment of gastroesophageal cancers (GEC). In the US, ICIs have established indications for second-line treatment of microsatellite unstable tumors, while their use in third-line settings w...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/23/5929 |
| _version_ | 1797508025220595712 |
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| author | Koosha Paydary Natalie Reizine Daniel V. T. Catenacci |
| author_facet | Koosha Paydary Natalie Reizine Daniel V. T. Catenacci |
| author_sort | Koosha Paydary |
| collection | DOAJ |
| description | To date, several trials have evaluated the safety and efficacy of immune-checkpoint inhibitors (ICI) for the treatment of gastroesophageal cancers (GEC). In the US, ICIs have established indications for second-line treatment of microsatellite unstable tumors, while their use in third-line settings was recently withdrawn. Notably, the use of ICIs for first-line therapy of GEC is rapidly evolving, which currently includes high PD-L1 expressing tumors, irrespective of HER2 status, and in the adjuvant setting after neoadjuvant chemoradiotherapy in select patients. In this article, we review the results of studies that have evaluated the utility of ICI in the third-line, second-line, first-line, and peri-operative treatment settings of GECs. Considerations should be made before making any cross-trial comparisons since these trials vary in chemotherapy backbone, anatomical and histological eligibility, biomarker assessment, PD-L1 diagnostic antibodies, and definition of PD-L1 positivity. Regardless, the totality of the data suggest that first-line ICI use may most benefit GEC patients with high PD-L1 combined positivity score (CPS) ≥5 or ≥10, irrespective of histology or anatomy. Moreover, although PD-L1 by CPS has a good negative predictive value for significant benefit from ICIs, it has a low positive predictive value. Therefore, there is a pressing need to identify better biomarkers to predict benefit from ICIs among these patients. |
| first_indexed | 2024-03-10T04:56:44Z |
| format | Article |
| id | doaj.art-f2b7e32cdfe8473da16e1154a5c6f0d0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:56:44Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f2b7e32cdfe8473da16e1154a5c6f0d02023-11-23T02:11:38ZengMDPI AGCancers2072-66942021-11-011323592910.3390/cancers13235929Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging EvidenceKoosha Paydary0Natalie Reizine1Daniel V. T. Catenacci2Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center and Biological Sciences, Chicago, IL 60637, USASection of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center and Biological Sciences, Chicago, IL 60637, USASection of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center and Biological Sciences, Chicago, IL 60637, USATo date, several trials have evaluated the safety and efficacy of immune-checkpoint inhibitors (ICI) for the treatment of gastroesophageal cancers (GEC). In the US, ICIs have established indications for second-line treatment of microsatellite unstable tumors, while their use in third-line settings was recently withdrawn. Notably, the use of ICIs for first-line therapy of GEC is rapidly evolving, which currently includes high PD-L1 expressing tumors, irrespective of HER2 status, and in the adjuvant setting after neoadjuvant chemoradiotherapy in select patients. In this article, we review the results of studies that have evaluated the utility of ICI in the third-line, second-line, first-line, and peri-operative treatment settings of GECs. Considerations should be made before making any cross-trial comparisons since these trials vary in chemotherapy backbone, anatomical and histological eligibility, biomarker assessment, PD-L1 diagnostic antibodies, and definition of PD-L1 positivity. Regardless, the totality of the data suggest that first-line ICI use may most benefit GEC patients with high PD-L1 combined positivity score (CPS) ≥5 or ≥10, irrespective of histology or anatomy. Moreover, although PD-L1 by CPS has a good negative predictive value for significant benefit from ICIs, it has a low positive predictive value. Therefore, there is a pressing need to identify better biomarkers to predict benefit from ICIs among these patients.https://www.mdpi.com/2072-6694/13/23/5929immune-checkpoint inhibitorgastroesophageal cancerprogrammed death ligand-1 |
| spellingShingle | Koosha Paydary Natalie Reizine Daniel V. T. Catenacci Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence Cancers immune-checkpoint inhibitor gastroesophageal cancer programmed death ligand-1 |
| title | Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence |
| title_full | Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence |
| title_fullStr | Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence |
| title_full_unstemmed | Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence |
| title_short | Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence |
| title_sort | immune checkpoint inhibition in the treatment of gastro esophageal cancer a closer look at the emerging evidence |
| topic | immune-checkpoint inhibitor gastroesophageal cancer programmed death ligand-1 |
| url | https://www.mdpi.com/2072-6694/13/23/5929 |
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