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A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial cancer
BACKGROUND AND OBJECTIVES: Endometrial cancer is a common malignancy and recurrences can be fatal. Although platinum-pretreated endometrial tumors are commonly treated with anthracyclines and taxanes, there is no current standard of care. Both immune checkpoint inhibitors (ICIs) and tyrosine kinase...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026109/ https://www.ncbi.nlm.nih.gov/pubmed/36950270 http://dx.doi.org/10.1177/17588359231157633 |
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author | Tinker, Anna V. Dhani, Neesha C. Ghatage, Prafull McLeod, Deanna Samouëlian, Vanessa Welch, Stephen A. Altman, Alon D. |
author_facet | Tinker, Anna V. Dhani, Neesha C. Ghatage, Prafull McLeod, Deanna Samouëlian, Vanessa Welch, Stephen A. Altman, Alon D. |
author_sort | Tinker, Anna V. |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Endometrial cancer is a common malignancy and recurrences can be fatal. Although platinum-pretreated endometrial tumors are commonly treated with anthracyclines and taxanes, there is no current standard of care. Both immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) have been extensively assessed in this setting, including tumors selected for DNA mismatch repair (MMR)/microsatellite instability (MSI) and programmed death-ligand 1 expression status. This review will provide evidence-based guidance on use of ICIs alone or in combination with TKIs in patients with pretreated advanced, persistent, or recurrent metastatic endometrial cancer. DATA SOURCES AND METHODS: Randomized phase II–III trials in unselected populations pretreated, recurrent, or metastatic endometrial cancer and phase I–II trials in biomarker selected populations were identified from PubMed as well as conference proceedings using the key search terms ‘immune checkpoint inhibitors’, ‘endometrial cancer’, and ‘advanced’. RESULTS: A total of nine eligible studies were identified assessing ICI monotherapy for biomarker-selected or ICI plus TKI combinations and a dual ICI regimen for biomarker-unselected patients with pretreated recurrent or metastatic endometrial cancer. In MMR/MSI-selected tumors, five phase I/II studies evaluated ICI monotherapy indicating benefit in these patients. Only the phase III KEYNOTE-775 trial reported a statistically significant overall survival improvement for the combination of pembrolizumab plus lenvatinib compared with docetaxel or paclitaxel regardless of MMR/MSI status. CONCLUSIONS: Pembrolizumab plus lenvatinib is indicated for patients with unselected pretreated metastatic endometrial cancer and pembrolizumab monotherapy is a preferred option for patients with MMRd/MSI-H tumors. |
format | Online Article Text |
id | pubmed-10026109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-100261092023-03-21 A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial cancer Tinker, Anna V. Dhani, Neesha C. Ghatage, Prafull McLeod, Deanna Samouëlian, Vanessa Welch, Stephen A. Altman, Alon D. Ther Adv Med Oncol Immunotherapy in Gynecological Cancers BACKGROUND AND OBJECTIVES: Endometrial cancer is a common malignancy and recurrences can be fatal. Although platinum-pretreated endometrial tumors are commonly treated with anthracyclines and taxanes, there is no current standard of care. Both immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) have been extensively assessed in this setting, including tumors selected for DNA mismatch repair (MMR)/microsatellite instability (MSI) and programmed death-ligand 1 expression status. This review will provide evidence-based guidance on use of ICIs alone or in combination with TKIs in patients with pretreated advanced, persistent, or recurrent metastatic endometrial cancer. DATA SOURCES AND METHODS: Randomized phase II–III trials in unselected populations pretreated, recurrent, or metastatic endometrial cancer and phase I–II trials in biomarker selected populations were identified from PubMed as well as conference proceedings using the key search terms ‘immune checkpoint inhibitors’, ‘endometrial cancer’, and ‘advanced’. RESULTS: A total of nine eligible studies were identified assessing ICI monotherapy for biomarker-selected or ICI plus TKI combinations and a dual ICI regimen for biomarker-unselected patients with pretreated recurrent or metastatic endometrial cancer. In MMR/MSI-selected tumors, five phase I/II studies evaluated ICI monotherapy indicating benefit in these patients. Only the phase III KEYNOTE-775 trial reported a statistically significant overall survival improvement for the combination of pembrolizumab plus lenvatinib compared with docetaxel or paclitaxel regardless of MMR/MSI status. CONCLUSIONS: Pembrolizumab plus lenvatinib is indicated for patients with unselected pretreated metastatic endometrial cancer and pembrolizumab monotherapy is a preferred option for patients with MMRd/MSI-H tumors. SAGE Publications 2023-03-18 /pmc/articles/PMC10026109/ /pubmed/36950270 http://dx.doi.org/10.1177/17588359231157633 Text en © The Author(s), 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Immunotherapy in Gynecological Cancers Tinker, Anna V. Dhani, Neesha C. Ghatage, Prafull McLeod, Deanna Samouëlian, Vanessa Welch, Stephen A. Altman, Alon D. A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial cancer |
title | A rapidly evolving landscape: immune checkpoint inhibitors in
pretreated metastatic endometrial cancer |
title_full | A rapidly evolving landscape: immune checkpoint inhibitors in
pretreated metastatic endometrial cancer |
title_fullStr | A rapidly evolving landscape: immune checkpoint inhibitors in
pretreated metastatic endometrial cancer |
title_full_unstemmed | A rapidly evolving landscape: immune checkpoint inhibitors in
pretreated metastatic endometrial cancer |
title_short | A rapidly evolving landscape: immune checkpoint inhibitors in
pretreated metastatic endometrial cancer |
title_sort | rapidly evolving landscape: immune checkpoint inhibitors in
pretreated metastatic endometrial cancer |
topic | Immunotherapy in Gynecological Cancers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026109/ https://www.ncbi.nlm.nih.gov/pubmed/36950270 http://dx.doi.org/10.1177/17588359231157633 |
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