Medical expert provides an overview of the recommended biomarker testing for endometrial cancer and the frontline treatment options available for patients with dMMR/MSI-high endometrial cancer.
Matthew A. Powell, MD: Welcome to Targeted Oncology™ Investigator Perspectives. We’re focusing on endometrial carcinoma [management] advances. I’m Matt Powell. I’m a gynecologic oncologist and director of the Division of Gynecologic Oncology at Siteman Cancer Center in St Louis, Missouri, part of Washington University Barnes-Jewish Hospital Medical System. We have an exciting review for you today.
I’d like to review biomarker testing and endometrial cancer. A lot’s been learned over the past decade since the TCGA [The Cancer Genome Atlas] taught us that there are 4 different types of endometrial cancers. And one of the focuses we have is on the defective mismatch repair [dMMR] population. But biomarker testing is a hot subject, and how do we determine what molecular class a patient’s tumor may be involved in, and what else should we be testing? All are important factors. Defective mismatch repair really came out as we looked for Lynch syndrome and [were] doing microsatellite instability [MSI] testing, trying to find inherited genetic disease. But as we learned, about one-third of patients have defective mismatch repair and most of that is from promoter methylation of the MLH1 gene. Now we can look for these mutations in our cancers with immunohistochemistry with next-generation sequencing, and these are available through a lot of different platforms, both locally with our pathologists and with several biomarker assays. As many of you know, throughout the world, many of the authoritative bodies have now recommended molecular testing for management of patients with endometrial cancer, and that includes trying to identify the polymerase epsilon mutation that drives a population [with] ultra[mutation]. I mentioned defective mismatch repair, and most of that’s done now with immunohistochemistry for proteins. Also, doing P53 gene staining or P53 mutation analysis can help us identify the serous-light group, otherwise called [the] copy number–high group.
Then there’s a group that’s left behind. And that’s the no particular or no specific molecular group, or the copy number–low group, that typically is the estrogen receptor–positive group. And that gives us the 4 separate categories in endometrial cancers. Certainly, other biomarkers are important as HER2 in breast cancer and gastric cancer. We know that’s important in endometrial cancer to target. It could be a target for current use [of] trastuzumab [and] maybe down the road for other HER2-directed strategies. NTRK fusions and other markers may be of interest as we have more and more areas where there’s a pan-tumor approval for use of different drugs, although that’s rare in endometrial cancer. When we look at whom to test, basically every patient should have that mismatch repair testing and likely P53 testing. Those are the easy ones to do and really help you stratify for that. When it comes to patients who need systemic therapy or have advanced-stage disease or recurrent disease, you want to think about having all this information available to you as you make treatment decisions, including the HER2, tumor mutational burden, and other aspects to help us understand who benefits from single-agent checkpoint inhibition or who requires combination therapy.
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