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A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial cancer

A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Therapeutic Advances in Medical Oncology SAGE

A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial cancer

19 pages

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References (118)

Publisher
SAGE
Copyright
© The Author(s), 2023
ISSN
1758-8340
eISSN
1758-8359
DOI
10.1177/17588359231157633
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Therapeutic Advances in Medical OncologySAGE

Published: Mar 1, 2023

Keywords: advanced; biomarker selection; endometrial cancer; immune checkpoint inhibitors; metastatic; pretreated

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