Skill Checkup: A Woman With Increasing Abdominal Pain, Nausea, Vomiting, and Ascites

Pamela Soliman, MD, MPH


April 21, 2022

Data have shown that dMMR predicts response to PD-1 blockade. In terms of biomarker-directed systemic therapy for the second-line treatment of endometrial cancer, PD-1 inhibitors represent an option for microsatellite instability-high (MSI-H)/dMMR endometrial tumors. The Food and Drug Administration (FDA) expanded the indication of pembrolizumab to include the treatment of unresectable or metastatic, MSI-H or dMMR solid tumors that have progressed following prior treatment and have no alternative treatment options. In addition, in a nonrandomized trial, dostarlimab was associated with clinically meaningful and durable antitumor activity for patients with dMMR mutation endometrial cancers after prior platinum-based chemotherapy.

In general, dMMR leads to the repeated sequences of mismatches, insertions and deletions, representing the most common cause of hereditary endometrial cancer. This phenomenon causes Lynch syndrome, which makes up around 2.5% of endometrial carcinomas. Therefore, screening of endometrial tumors for defective dMMR via immunochemistry and/or MSI is used to identify which patients should undergo mutation testing for Lynch syndrome, an autosomal dominant mutation in the DNA of MMR proteins (MLH1, MSH2, MSH6 or PMS2, and EPCAM). Although the most frequently occurring histologic subtype of endometrial cancer is endometrioid adenocarcinoma, Lynch syndrome is associated with more heterogenous histologies.

According to National Comprehensive Cancer Network (NCCN) guidelines, dostarlimab-gxly is indicated for patients with dMMR/MSI-H recurrent or advanced endometrial carcinoma that has progressed on or following prior treatment with a platinum-containing regimen, a clinical scenario represented in this case.


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