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Systemic Treatment Strategies Beyond Chemotherapy in Recurrent or Advanced Endometrial Cancer: A Systematic Review
István Madár1,2, Anett Szabó1,3, Bianca Golzio Navarro Cavalcante1
1Centre for Translational Medicine, Semmelweis University, 1088 Budapest, Hungary.
Cancers
|July 15, 2026
Summary
Adding immune checkpoint inhibitors (ICIs) to chemotherapy significantly improves survival for advanced endometrial cancer (EC), especially in mismatch repair-deficient (MMRd) tumors. Hormonal and targeted therapies offer alternative options, requiring better patient stratification for optimal outcomes.
Area of Science:
- Gynecologic Oncology
- Medical Oncology
- Translational Research
Background:
- Optimal systemic treatment for recurrent or advanced endometrial cancer (EC) remains uncertain, particularly in the second-line setting.
- Standard first-line chemotherapy has limited efficacy.
- Emerging therapies include immune checkpoint inhibitors (ICIs), hormonal therapies, and targeted agents.
Purpose of the Study:
- To systematically evaluate the efficacy and safety of systemic therapies beyond standard chemotherapy for recurrent or advanced EC.
- Focus on progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs).
Main Methods:
- Systematic review and meta-analysis of RCTs, prospective, and retrospective studies up to June 2024.
- Included studies evaluating chemotherapy, hormonal therapy, targeted agents, and ICIs in recurrent or advanced EC.
- Primary outcomes: PFS and OS; Secondary outcome: grade ≥ 3 TRAEs.
Main Results:
- Combining chemotherapy with ICIs significantly improved PFS and OS in mismatch repair-deficient (MMRd) EC patients (mPFS: 22.73 months vs. 8.39 months).
- In mismatch repair-proficient (MMRp) patients, ICI addition showed a smaller PFS benefit (mPFS: 10.18 months vs. 9.4 months).
- Exploratory analyses examined hormonal and targeted therapies, including lenvatinib plus pembrolizumab.
Conclusions:
- Chemotherapy combined with ICIs demonstrates the most favorable survival outcomes, particularly for MMRd endometrial cancer.
- Hormonal and targeted therapies are potential options, with efficacy dependent on tumor biology.
- Improved patient stratification is crucial for optimizing treatment selection in advanced EC.
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