What role does molecular testing play in guiding an endometrial cancer treatment plan? Expert Dr. Dario Roque explains the essential tests, reviews biomarkers that impact care, and discusses how advances in personalized medicine are helping to improve outcomes for patients.
Dr. Dario Roque is a Gynecologic Oncologist and an Associate Professor of Gynecologic Oncology at Northwestern Medicine. Learn more about Dr. Roque.
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Transcript
Katherine Banwell:
Dr. Roque, how has molecular or genetic testing changed the way you treat endometrial cancer?
Dr. Dario Roque:
Yeah, so one thing that we routinely test for is what’s called mismatch repair proteins, or MMR for short, and patients who have that deficiency, we do know they tend to have better responses to immunotherapy. So, the dostarlimab-gxly (Jemperli), the pembrolizumab (Keytruda) drugs, that I was previously discussing, those patients, we anticipate that they will have a good response to those drugs. So, that’s the reason we test for those markers because it helps us determine this is someone that will derive significant benefit from immunotherapy. Another molecular test that we routinely do for patients with endometrial cancer is something called HER2.
And patients who have that marker, if needed, they are eligible for HER2-targeted therapies. There are two drugs that we routinely use for those patients. One of them is called Herceptin or trastuzumab. The other one is called fam-trastuzumab deruxtecan-nxki (Enhertu). I’m not going to talk about the generic name from now on because it’s very complicated. It’s trastuzumab deruxtecan, if we need to talk about it, but I can refer to it just as Enhertu.
Katherine Banwell:
So, you mentioned HER2; how do biomarkers like HER2 status or p53 status influence treatment planning?
Dr. Dario Roque:
So, usually it depends a lot on the stage. I think normally the stages will primarily dictate a lot of the treatment, and then certainly patients that have more advanced stage that we think would benefit from having systemic therapy.
This is where having the molecular markers helps significantly. For example, if we have a patient that we do know will require systemic therapy, and that patient has an MMR deficiency in the mismatch repair proteins, that is someone that we would very strongly recommend receiving immunotherapy as part of their treatment regimen versus a patient who does not have those mismatch repair markers but is HER2-positive. Then in that patient, we might say, let’s use a HER2-targeting agent instead of the immunotherapy.
As time goes on, I anticipate there will be more and more of these markers that can help us personalize the treatment more to the individual patients, but that is how we are using them currently.
Katherine Banwell:
Is there emerging research that is showing promise?
Dr. Dario Roque:
Yeah, absolutely. There is a project right now looking at patients that are what are called p53 wild type.
So, p53 is a mutation that we see frequently in patients with endometrial cancer that have a serious histological subtype, so that’s a specific cell type. There is a drug right now that is being studied in patients that are p53 wild type that seems to be promising in that specific patient population. There is also ongoing research looking at other types of classes of drugs that are called antibody drug conjugates. Enhertu, which I discussed earlier, is one of those types of drugs. And antibody drug conjugates, they work as they target a specific marker on the cancer cell and then deliver a chemotherapy drug directly to those cells.
There are a number of targets that are being studied currently, including folate receptor alpha, B7-H4, so there are different markers that are being studied for drugs that are currently in development.