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

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Video Summary

This symposium segment focused on treatment strategies for mismatch repair proficient (PMMR) endometrial cancer, a biologically heterogeneous group that lacks a single standard approach. Dr. Randall reviewed frontline immune checkpoint inhibitor trials and emphasized that PMMR tumors benefit less than DMMR tumors, though mature GY018 data now support use of immunotherapy in PMMR disease.<br /><br />A real patient case illustrated the challenge of recurrent PMMR carcinosarcoma after surgery, chemotherapy, and later metastatic relapse. The discussion then explored emerging options: adding PARP inhibitors to immunotherapy, with DUO-E and RUBY part 2 suggesting progression-free survival benefit and possible ctDNA-guided selection; targeting VEGF with lenvatinib/pembrolizumab, which remains the most evidence-supported option for recurrent PMMR disease; and additional approaches under study, including bevacizumab, HER2-directed therapy, and several antibody-drug conjugates (ADCs) against HER2, TROP2, B7H4, and folate receptor alpha.<br /><br />Other non-ADC strategies included selenexor, endocrine therapy combinations, and mTOR/metabolic approaches. The speakers stressed that platinum-free interval is not a reliable guide in endometrial cancer, unlike ovarian cancer. Overall, the key message was that PMMR endometrial cancer requires biomarker-driven, individualized treatment, with lenvatinib/pembrolizumab currently the strongest standard option and many promising strategies in development.

Keywords

PMMR endometrial cancer

immune checkpoint inhibitor

lenvatinib pembrolizumab

PARP inhibitors

mismatch repair proficient

carcinosarcoma recurrence

biomarker-driven therapy

antibody-drug conjugates

ctDNA-guided selection