Impact of chemotherapy on patients with mismatch repair deficient advanced endometrial carcinomas-a meta-analysis
Journal Title
JNCI Cancer Spectrum
Publication Type
Online publication before print
Abstract
INTRODUCTION: Chemo-immunotherapy is standard of care for women with recurrent or advanced mismatch repair deficient (dMMR) endometrial carcinomas (EC). However, it is uncertain whether patients with dMMR advanced or recurrent EC derive less benefit from chemotherapy than those with mismatch repair proficient (pMMR) EC. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) in advanced/recurrent EC to determine the difference in the benefit of chemotherapy in dMMR vs pMMR EC. Data on chemotherapy outcomes including objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were retrieved. We pooled these data using the inverse variance method and examined subgroup difference by MMR status. We also compared differences in PFS and OS outcomes by creating individual patient data from the Kaplan-Meier curves of trial publications for sensitivity analyses. RESULTS: A total of five RCTs with 1137 participants (dMMR, 26%; pMMR, 74%) were included. All participants were treated with carboplatin-based chemotherapy. There was no difference between the dMMR and pMMR subgroups for ORR (66.5% vs 64.0%, P = .20 for subgroup difference), PFS (HR 0.93, 95% CI 0.77-1.12, P = .44; median PFS 7.6 vs 9.5 months) or OS (HR 1.03, 95% CI 0.73-1.44, P = .88; median OS not reached vs 28.6 months). CONCLUSIONS: ORR, PFS and OS were similar among those with dMMR vs pMMR endometrial cancer treated with front-line, platinum-doublet chemotherapy in randomized clinical trials. These findings reinforce the importance of combining chemotherapy together with immune checkpoint inhibitors until the results of trials comparing immune checkpoint therapy alone with combination therapy are available.
Keywords
Mmr; chemotherapy; endometrial cancer; immune checkpoint inhibition; mismatch repair
Department(s)
Medical Oncology
Open Access at Publisher's Site
https://doi.org/10.1093/jncics/pkae101
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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