Optimizing Therapy for MMR-Proficient Endometrial Cancer

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This segment examines the DUO trial results presented at SGO 2025, which investigated the combination of durvalumab (anti–PD-L1) with olaparib (PARP inhibitor) in early-stage endometrial cancer. The trial enrolled over 700 patients and confirmed the significant benefit of PD-L1 inhibition in adjuvant endometrial cancer treatment, regardless of microsatellite instability status. While the addition of olaparib showed promise in certain subgroups, particularly mismatch repair–proficient patients and those with negative circulating tumor DNA, the study was not powered for these subgroup analyses, making the findings hypothesis-generating rather than practice-changing.

The discussion reveals ongoing uncertainty about incorporating PARP inhibitors into routine endometrial cancer care, with experts acknowledging the theoretical rationale while awaiting more definitive data. The conversation explores the biological basis for PARP inhibitor efficacy in specific subgroups, particularly the copy number high, p53-mutated subtype that may harbor DNA repair deficiencies similar to those seen in ovarian cancer. However, panelists emphasize the need for confirmatory studies before routine clinical implementation.

A practical clinical scenario emerges regarding ambiguous pathology cases where distinction between high-grade serous ovarian and endometrial cancers is challenging. The discussion explores whether PARP inhibitor addition might be justified in such cases, given the established benefit in ovarian cancer maintenance therapy. This highlights the complexity of treatment decisions when pathologic classification is uncertain and demonstrates the evolving nature of precision medicine approaches in gynecologic oncology, where treatment decisions increasingly depend on molecular characteristics rather than traditional pathologic features alone.