SIENDO Study: Long-Term Safety and Efficacy of Selinexor Maintenance in Endometrial Cancer

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This segment provides a comprehensive overview of current treatment options for recurrent endometrial cancer, highlighting the dramatic expansion of therapeutic choices available to patients. The discussion covers combination regimens including carboplatin/paclitaxel with pembrolizumab (Keytruda) or dostarlimab, representing standard immunotherapy combinations for treatment-naive patients. Additionally, targeted therapies like trastuzumab deruxtecan (T-DXd) for HER2-positive tumors and various NTRK inhibitors for NTRK fusion–positive cancers demonstrate the growing importance of precision medicine in endometrial cancer treatment.

The conversation extensively addresses treatment decisions for mismatch repair proficient (pMMR) versus deficient (dMMR) tumors, with particular focus on the RUBY trial data showing significant benefits in dMMR patients. Experts discuss their evolving approaches to immunotherapy maintenance, with many becoming more comfortable treating pMMR patients based on compelling hazard ratios, while considering p53 mutation status as a key biomarker for treatment selection. The lenvatinib plus pembrolizumab combination emerges as an important option for pMMR patients, though experts debate optimal sequencing strategies.

The segment also explores the controversial topic of immunotherapy retreatment after initial immunotherapy failure. Practitioners share varying approaches to using different immunotherapy regimens sequentially, with some viewing lenvatinib/pembrolizumab as distinct from chemotherapy/immunotherapy combinations. The discussion emphasizes the distinction between measurable and nonmeasurable disease, noting that immunotherapy combinations are primarily beneficial in measurable disease settings, while nonmeasurable disease shows limited benefit except in the dMMR subgroup.