Precision in Endometrial Cancer: Personalized Treatment Strategies for pMMR and dMMR Endometrial Cancer-Charting the Course: Treatment Approaches for pMMR Endometrial Cancer

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Video Summary

At the 2024 International Gynecologic Cancer Society meeting, experts discussed advances in managing advanced or recurrent endometrial cancer, focusing on molecular subclassifications—especially mismatch repair (MMR) status—and their impact on treatment. Dr. Angelica Rodriguez highlighted second-line therapies based on MMR proficiency: immune checkpoint inhibitors (IO) alone show nearly 50% response in MMR-deficient patients, while MMR-proficient patients benefit more from lenvatinib plus pembrolizumab due to better response and survival. Treatment sequencing now demands molecular profiling to guide therapy, including testing for HER2, hormone receptors, TP53 status, and emerging biomarkers like TROP-2. Case studies demonstrated the use of targeted therapies such as trastuzumab deruxtecan for HER2-positive tumors, resulting in durable responses. Discussants emphasized the necessity of biomarker testing to personalize treatment, although access and reimbursement challenges persist globally. They debated optimal dosing strategies for lenvatinib, underscoring starting at full dose for efficacy followed by dose adjustments. The panel also addressed retreatment strategies with immunotherapy (IO after IO), suggesting possible benefits especially in MMR-deficient tumors. Tumor heterogeneity and the potential need for repeat molecular profiling at recurrence were discussed, as tumor molecular profiles may shift over time. Finally, the rise of antibody-drug conjugates (ADCs) represents a promising new therapeutic frontier, though further research is needed to understand mechanisms, resistance, and toxicity in endometrial cancer treatment.

Keywords

endometrial cancer

mismatch repair (MMR) status

immune checkpoint inhibitors

lenvatinib plus pembrolizumab

molecular profiling

HER2-targeted therapy

antibody-drug conjugates (ADCs)