At the 2023 Society of Gynecological Oncology’s Annual Meeting on Women’s Cancer, Sarah Lee, MD, NYU Langone Health, New York, NY, discusses a study examining the potential effect high tumor mutational burden, high microsatellite stability, and mismatch repair deficiency may have on the clinical outcomes of patients with endometrial cancer.

Transcript

Hi, my name is Sarah Lee. I'm a gynecologic oncology fellow at NYU Langone Health, and we are talking about our plenary that we gave at the Society of Gynecological Oncology’s Annual Meeting on Women’s Cancer in Tampa in March of 2023, titled “Clinical Outcomes of Patients with High Tumor Mutational Burden, High Microsatellite Instability, and Mismatch Repair Deficiency in a Multi-Institutional Endometrial Cancer Consortium.” Essentially our study was done because in the last 5 years or so, the indications for immunotherapy for patients with endometrial cancer have really grown to include patients with high tumor mutational burden (TMB), high microsatellite instability (MSI), and mismatch repair deficiency (dMMR), with pembrolizumab and dostarlimab both getting FDA approvals, both regular and accelerated. In the era of increasing tumor molecular profiling, we were really interested in the relationship between high TMB and MSI-high/dMMR tumors.

This was a multi-institutional endometrial cancer consortium. The endometrial cancer consortium, where the official title is the Endometrial Cancer Molecularly Targeted Therapy Consortium, was founded at Duke University, currently includes 22 participating institutions from across the United States, and it's a prospective and retrospective data repository of patients with endometrial cancers.

For this specific study, we included patients that underwent tumor molecular profiling that had advanced recurrent endometrial tumors, included all histologies except for sarcomas, and patients that underwent specifically TMB testing and had had underwent TMB testing were included in the study. We had 742 patients across 13 institutions. Of those patients, 2% had TMB-high only, 8% had MSI-high/dMMR only, and 12% had both.

The main findings of our study really were that Black patients were less likely to be MSI-high and dMMR. Of the Black patients included in our study, only 3% were MSI high and dMMR versus 10% of non-Black patients. Not only that, 29% of patients with TMB-high were Black versus only 8% of those with MSI-high/dMMR were Black. Patients that were TMB-high only, so these are patients that did not have MSI-high or dMMR, these patients, although there's only 14 of them included in our study, they had a higher rate of higher risk histology. In the overall group, in the patients that had TMB-high and MSI-high/dMMR, about 3/4 of these patients had endometrioid histology. Compare that only 56% of patients with TMB-high alone had endometrial histology, and the majority of those had high grade.

Not only that, when we looked at overall survival, patients with any of these biomarkers had improved overall survival compared to those without the biomarkers. When we stratified the overall survival analysis by race and looked at the biomarker status, the patients that did the worst were Black patients without any biomarkers.

To wrap up, the conclusions of our study are that more work needs to be done to determine the molecular makeup of these high tumor mutational burden patients. This is a multi-institutional study, so definitely more work needs to be done to look at the patients who are TMB-high alone.

Source:

Lee S. “Clinical outcomes of patients with high tumor mutational burden, high microsatellite stability, and mismatch repair deficiency in a multi-institutional endometrial cancer consortium.” Presented at: SGO Annual Meeting on Women's Cancer; March 25-28, 2023; Tampa, FL