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Anti-programmed Death-1 Immunotherapy for Endometrial Cancer with Microsatellite Instability-High Tumors
Janelle Sobecki-Rausch1, Lisa Barroilhet2
1Division of Gynecologic Oncology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53792, USA. janellesobecki@gmail.com.
Opinion Statement:
Among gynecologic malignancies, mismatch repair-deficient endometrial cancers show the greatest response to anti-programmed cell death-1 (PD-1) antibodies, such as pembrolizumab. Routine immunohistochemical (IHC) and molecular testing should be performed on all endometrial cancers at the time of diagnosis in order to identify endometrial cancers with mismatch repair deficiency that may show improved response to anti-PD-1 therapy in the progressive or metastatic setting. Institutional effort to enroll patients in clinical trials investigating the use of immune checkpoint inhibitors in endometrial cancer should be prioritized.
Insights
Mismatch repair-deficient endometrial cancers respond best to anti-programmed cell death-1 (PD-1) therapies. Testing all endometrial cancers for mismatch repair deficiency at diagnosis can identify patients who may benefit from these advanced treatments.
Area of Science:
- Gynecologic Oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- Endometrial cancer is a common gynecologic malignancy.
- Mismatch repair deficiency (dMMR) is a key biomarker in cancer immunotherapy.
- Anti-programmed cell death-1 (PD-1) antibodies offer a novel therapeutic avenue.
Purpose of the Study:
- To highlight the significant response of dMMR endometrial cancers to anti-PD-1 therapy.
- To advocate for routine diagnostic testing for dMMR in all endometrial cancers.
- To emphasize the potential of immunotherapy in advanced or metastatic endometrial cancer.
Main Methods:
- Immunohistochemical (IHC) testing for mismatch repair proteins.
- Molecular testing for microsatellite instability.
- Review of clinical responses to anti-PD-1 antibodies like pembrolizumab.
Main Results:
- dMMR status is a strong predictor of response to anti-PD-1 therapy in endometrial cancer.
- Patients with dMMR endometrial cancers demonstrate the greatest clinical benefit.
Conclusions:
- Routine IHC and molecular testing for dMMR should be standard practice for all endometrial cancer diagnoses.
- Identifying dMMR status allows for targeted use of anti-PD-1 therapy in progressive or metastatic settings.
- Prioritizing clinical trials for immune checkpoint inhibitors in endometrial cancer is crucial.
