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PD-1/PD-L1 inhibitors in endometrial cancer with high microsatellite instability: a Kaplan-Meier-derived patient data
Francisco Cezar Aquino de Moraes1, Maria Eduarda Cavalcanti Souza2, Maria Isadora Rodrigues Carlos3
1Department of Molecular Biology, Federal University of Pará (UFPA), Belém, Brazil.
Introduction:
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of solid tumors. This meta-analysis of randomized controlled trials aimed to assess the survival benefit of anti-PD-1/PD-L1 therapies in women with advanced or recurrent endometrial cancer (EC) and mismatch repair deficiency (dMMR).
Methods:
A systematic search was conducted in PubMed, Scopus, Cochrane, and Web of Science databases to compare PD-1/PD-L1 inhibitors versus standard therapy in patients with advanced/recurrent EC. Studies were screened based on predefined inclusion/exclusion criteria. Risk of bias was assessed using the Cochrane Risk of Bias Tool. We used DerSimonian and Laird random-effects models to estimate hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs).
Results:
Five studies including 2,739 patients were analyzed, with 627 (22.90%) having dMMR tumors. ICIs significantly improved progression-free survival (HR 0.35; 95% CI 0.28-0.44) and overall survival (HR 0.40; 95% CI 0.28-0.57) in dMMR patients. No significant difference was found in objective response rate (RR 1.72; 95% CI 0.88-3.36).
Conclusions:
The addition of immunotherapy for treating patients with advanced or recurrent endometrial cancer with dMMR and high microsatellite instability significantly improved PFS and OS outcomes.
Registration:
PROSPERO (CRD22057890200).
Insights
Immune checkpoint inhibitors (ICIs) significantly improved survival for women with advanced or recurrent endometrial cancer (EC) who have mismatch repair deficiency (dMMR). This immunotherapy approach enhances progression-free and overall survival in dMMR EC patients.
Area of Science:
- Oncology
- Immunotherapy
- Gynecologic Oncology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed solid tumor treatment.
- Endometrial cancer (EC) management, particularly advanced or recurrent stages, benefits from novel therapeutic strategies.
- Mismatch repair deficiency (dMMR) is a key biomarker in EC, influencing treatment response.
Purpose of the Study:
- To evaluate the survival benefits of anti-PD-1/PD-L1 therapies in patients with advanced or recurrent endometrial cancer (EC) and mismatch repair deficiency (dMMR).
- To conduct a meta-analysis of randomized controlled trials (RCTs) comparing ICIs with standard therapy in this specific patient population.
Main Methods:
- A systematic literature search was performed across major databases (PubMed, Scopus, Cochrane, Web of Science).
- Randomized controlled trials comparing PD-1/PD-L1 inhibitors with standard therapy in advanced/recurrent EC patients were included.
- Hazard ratios (HRs) and risk ratios (RRs) were estimated using random-effects models, with risk of bias assessed by the Cochrane Risk of Bias Tool.
Main Results:
- Analysis of five studies involving 2,739 patients revealed that 627 (22.90%) had dMMR tumors.
- ICIs demonstrated a significant improvement in progression-free survival (HR 0.35; 95% CI 0.28-0.44) and overall survival (HR 0.40; 95% CI 0.28-0.57) in dMMR EC patients.
- No statistically significant difference was observed in objective response rate (RR 1.72; 95% CI 0.88-3.36).
Conclusions:
- The addition of immunotherapy significantly enhances progression-free survival (PFS) and overall survival (OS) outcomes for patients with advanced or recurrent EC characterized by dMMR and high microsatellite instability.
- Anti-PD-1/PD-L1 therapies represent a valuable treatment option for this subset of endometrial cancer patients.
