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Review
. 2023 Mar 18:15:17588359231157633.
doi: 10.1177/17588359231157633. eCollection 2023.

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

Anna V Tinker  1 , Neesha C Dhani  2 , Prafull Ghatage  3 , Deanna McLeod  4 , Vanessa Samouëlian  5 , Stephen A Welch  6 , Alon D Altman  7
Affiliations
Review

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

Anna V Tinker et al. Ther Adv Med Oncol. .

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.

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

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Conflict of interest statement

Alon Altman reports grants AstraZeneca, Pfizer, Clovis, CCMB foundation, Canadian Clinical Trials Group, Merck, and GSK, outside the submitted work. He has also served in an advisory role for AstraZeneca, Merck, and GSK and has received speaker fees from AstraZeneca and Merck. Neesha C. Dhani has nothing to disclose. Prafull Ghatage has served in a consultancy or advisory role for Eisai, AstraZeneca, and GSK and has received research funding from AstraZeneca. Deanna McLeod has nothing to disclose. Vanessa Samouëlian has served in a consultancy or advisory role for GSK and Merck and has received honoraria from Merck and GSK. Anna Tinker has served in a consultancy or advisory role for Eisai, AstraZeneca, GSK, has received honoraria from Eisai, Merck, AstraZeneca, GSK, and has received research funding from AstraZeneca. Stephen A. Welch has served in a consultancy or advisory role for Merck, Eisai, GSK, and has received honoraria from Merck, Eisai, GSK.

Figures

Figure 1.
Figure 1.
PRISMA diagram of eligible studies. aPrimary reports of eligible studies that were not identified through database search. ASCO, American Society of Clinical Oncology; ESMO, European Society for Medical Oncology; ICI, immune checkpoint inhibitor; n, number of reports or studies; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SGO, Society of Gynecologic Oncology.
Figure 2.
Figure 2.
TRAE rates in the phase III trial of pembrolizumab plus lenvatinib and average TRAE rates across multiple single ICI trials. TRAEs included were those reported for the pembrolizumab plus lenvatinib arm of the KEYNOTE-775 trial and/or any TRAE reported in two or more single ICI trials. Any cause AE rate data were used when TRAE rate data were not available (PHAEDRA trial). ALT, alanine transaminase; AST, aspartate transaminase; ICI, immune checkpoint inhibitor; Lenva, lenvatinib; MI, mucosal inflammation; NR, not reported (in any ICI trial [green] or in the KEYNOTE-775 trial [blue]); Pembro, pembrolizumab; PPE, palmar-plantar erythrodysesthesia; TRAE, treatment-related adverse event; WBC, white blood cell.
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