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Meta-Analysis
. 2024 Nov 1;8(6):pkae101.
doi: 10.1093/jncics/pkae101.

Impact of chemotherapy on patients with mismatch repair deficient advanced endometrial carcinomas-a meta-analysis

Angelina Tjokrowidjaja  1   2 , Peey-Sei Kok  1   2 , Yoland C Antill  2   3 , Clare L Scott  2   4   5 , Linda R Mileshkin  2   5 , Michael L Friedlander  2   6 , Chee K Lee  1   2
Affiliations
Meta-Analysis

Impact of chemotherapy on patients with mismatch repair deficient advanced endometrial carcinomas-a meta-analysis

Angelina Tjokrowidjaja et al. JNCI Cancer Spectr. .

Abstract

Background: Chemo-immunotherapy is standard of care for women with recurrent or advanced mismatch repair deficient endometrial carcinoma. However, it is uncertain whether patients with mismatch repair deficient advanced or recurrent endometrial carcinoma derive less benefit from chemotherapy than those with mismatch repair proficient endometrial carcinoma.

Methods: We performed a meta-analysis of randomized controlled trials (RCTs) in advanced or recurrent endometrial carcinoma to determine the difference in the benefit of chemotherapy in mismatch repair deficient vs mismatch repair proficient endometrial carcinoma. Data on chemotherapy outcomes including objective response rate, progression-free survival (PFS), and overall survival were retrieved. We pooled these data using the inverse variance method and examined subgroup difference by mismatch repair status. We also compared differences in PFS and overall survival outcomes by creating individual patient data from the Kaplan-Meier curves of trial publications for sensitivity analyses.

Results: A total of 5 RCTs with 1137 participants (mismatch repair deficient, 26%; mismatch repair proficient, 74%) were included. All participants were treated with carboplatin-based chemotherapy. There was no difference between the mismatch repair deficient and mismatch repair proficient subgroups for objective response rate (66.5% vs 64.0%; P = .20 for subgroup difference), PFS (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.77 to 1.12; P = .44; median PFS = 7.6 vs 9.5 months) or overall survival (HR = 1.03, 95% CI = 0.73 to 1.44; P = .88; median overall survival = not reached vs 28.6 months).

Conclusions: Objective response rate, PFS, and overall survival were similar among those with mismatch repair deficient vs mismatch repair proficient endometrial cancer treated with front-line, platinum-doublet chemotherapy in RCTs. 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.

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Conflict of interest statement

P-S. Kok reports advisory boards honoraria from MSD, research funding (institution) from AstraZeneca, support for attending meetings from AstraZeneca and Pfizer.

A. Tjokrowidjaja reports honoraria from MSD, research funding (institution) from AstraZeneca, support for attending meetings from GSK.

M.L. Friedlander reports consulting fees from Novartis, AstraZeneca, MSD, Lilly, GSK, Takeda; honoraria from AstraZeneca, GSK, MSD; grants (institution) from AstraZeneca, Novartis, Beigene; participation on a data safety monitoring board or advisory board for AGITG; support for attending meetings from AstraZeneca.

C.K. Lee reports honoraria from AstraZeneca, Roche, Amgen, GSK, Merck KGA, Novartis, Pfizer, Janssen; grants (institution) from AstraZeneca, Roche, Amgen, Merck KGA; support for attending meetings from AstraZeneca.

Y.C. Antill reports research support, advisory role, and speakers bureau from AstraZeneca, advisory role and speakers bureau GSK, MSD and Eisai.

C.L. Scott reports advisory boards (no honoraria) for AstraZeneca, Clovis Oncology, Roche, Eisai Inc, Sierra Oncology, Takeda, MSD and GSK; grant/research support from Clovis Oncology, Eisai Inc, Sierra Oncology, Roche, Beigene, AstraZeneca and Boehringer Ingelheim; and travel support from AstraZeneca and MSD.

L.R. Mileshkin reports honoraria from GSK, advisory board participation (with no honoraria) for AstraZeneca, GSK and Eisai; grant/research support from Beigene and support for attending meetings from Roche.

Figures

Figure 1.
Figure 1.
Study flow diagram. This flow diagram illustrates the inclusion and exclusion of studies. MMR = mismatch repair; MSI = microsatellite instability; RCT = randomized controlled trial.
Figure 2.
Figure 2.
Objective response rate, according to mismatch repair status. CI = confidence interval; dMMR = mismatch repair deficient; pMMR = mismatch repair proficient.
Figure 3.
Figure 3.
Forest plots of treatment effect of chemotherapy on survival, according to mismatch repair status. A) Progression-free survival, (B) overall survival. CI = confidence interval; dMMR= mismatch repair deficient; pMMR = mismatch repair proficient.
Figure 4.
Figure 4.
Kaplan–Meier curves, based on mismatch repair status and trials. A) Progression-free survival, (B) overall survival. CI = confidence interval; dMMR= mismatch repair deficient; HR = hazard ratio; OS = overall survival; PFS = progression-free survival; pMMR= mismatch repair proficient.
See this image and copyright information in PMC

References

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