Overview of Molecular Testing in Endometrial Carcinoma

EP: 1.Patient Case 1: MMRp Recurrent Endometrial Carcinoma

EP: 2.MMRp Recurrent Endometrial Carcinoma: What is a Typical Patient Presentation?

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EP: 3.Overview of Molecular Testing in Endometrial Carcinoma

EP: 4.Identifying Recurrence in Patients With Endometrial Carcinoma

EP: 5.Treatment Options for pMMR Recurrent EC: KEYNOTE 775

EP: 6.Real-World Use of Lenvatinib + Pembrolizumab in Patients With pMMR Recurrent EC

EP: 7.pMMR Recurrent EC: Optimal Selection and Sequencing of Therapy

EP: 8.Patient Case 2: dMMR Recurrent Endometrial Carcinoma

EP: 9.Pembrolizumab in dMMR Recurrent EC: Data From KEYNOTE-158

EP: 10.Dostarlimab in dMMR Recurrent EC: Data From GARNET

EP: 11.dMMR Recurrent EC: Practical Advice on Adverse Event Management

EP: 12.Patient Case 3: Metastatic Uterine Serous Carcinoma

EP: 13.Novel Triplet Therapy in Patients With Metastatic Uterine Serous Carcinoma

EP: 14.Novel Treatment Strategies in Endometrial Cancer

Transcript:

Michael J. Birrer, MD, PhD: I’ll be honest with you, Rob, this has evolved fast. MMR [mismatch repair] testing is done in-house in the pathology suite, so that is absolutely standard and there’s no issue about that. But we’re routinely now sending it out to commercial platforms, which are going to give us a panel, and will also give us LOH [loss of heterozygosity], for what that’s worth in this tumor, and we will get NTRK gene fusions, which frankly are pretty darn rare, but it’s worth knowing about them. I’ll say tumor mutational burden, we don’t reach out to, unless it’s on that panel.

Robert L. Coleman, MD, FACOG, FACS: I think they’re becoming more comprehensive as time goes on because more of these are starting to show up with predictive biomarkers, although HER2 is often looked at from the standpoint of amplification. But now with the potential availability of studies that are looking for less high expression levels, like we see with T-DXd [trastuzumab deruxtecan] and some of the other antibody-drug conjugates that are coming, we may even see this expanded further.

Michael J. Birrer, MD, PhD: As you know, although we can’t target it, there’s accumulating evidence that TP53 mutations in some of these cases are a poor prognostic feature. So maybe it’s something you want to know; it’s going to show up in the panels.

Robert L. Coleman, MD, FACOG, FACS: That’s right. It’s a great segue to the clinical trials that are starting to emerge looking at various ways that require that TP53 not be mutated, so the TP53 wild-type patients are now having opportunities for participation in clinical trials that are looking down that angle. There’s lots of information to be done with that. Before I leave this, one question, I was talking to a friend of mine from Spain yesterday about the sampling they do. They do as much genetic annotation as they can on the EMB [endometrial biopsy]. I’m curious, is that an approach you guys do in your shop?

Michael J. Birrer, MD, PhD: Yes, I would say we basically approach it the same way. The problem as we know in the EMB is sometimes there’s just not enough material to do all of it. And so we try to prioritize, and the IHC [immunohistochemistry] for the 4 proteins that define mismatch repair and potentially Lynch [syndrome] becomes the priority. But if there’s enough material, yes, we get it going….

Robert L. Coleman, MD, FACOG, FACS: Right. Kimberly, and at your place?

Kimberly Halla, MSN, FNP-C: Absolutely, the same thing. We try to get as much as we can from that. We want to start these treatments early, we want to make sure we’re getting the right targeted therapy for these patients, absolutely.

Robert L. Coleman, MD, FACOG, FACS: OK, excellent. I’ll ask, Mike, you touched on it briefly about Lynch. When do you bring in a genetic counselor? And that’s hard because we don’t have a lot of genetic counselors. I think you’ve got 4 in the entire state of Arkansas? It’s hard.

Michael J. Birrer, MD, PhD: Yes. We usually get a search firm to look for our counselor, it’s tough. We triage it, in other words, there are a lot of places that will say they won’t do the testing unless a genetic counselor is involved. We’ll start all the testing. If it’s positive for mismatch repair, and there is a possibility of Lynch, then we bring the genetic counselor in. We might even send off the blood to look for germline [mutations] before we get the counselor. When I was at Massachusetts General [Hospital], you couldn’t send out the germline test unless the genetic counselor did. That’s not the case here. But I do believe in genetic counseling because there are a lot of emotional issues, a lot of subtleties involved, so we want that expertise.

Robert L. Coleman, MD, FACOG, FACS: I don’t know all the syndromes. To be honest with you, I think I always have to keep looking it up. Kimberly, in your shop, how do you guys handle the genetic counseling?

Kimberly Halla, MSN, FNP-C: I would love to say that we have a genetic counselor available to us at all time, but much like the other industry, we just don’t. So many of my providers will do the basic kind of discussions, and when things come up positive, then we will reach out to our genetic counselor. But they’re slim, just like many of us. But with the use of telehealth, we’re able to capture a lot more of that as well.

Michael J. Birrer, MD, PhD: Yes. I think that’s a great point, Kimberly, which I didn’t mention. But with COVID-19, we shifted to essentially counseling at a distance, and there are now a number of commercial firms that do counseling from somewhere else. It’s probably a field that can do counseling at a distance. It works.

Robert L. Coleman, MD, FACOG, FACS: Yes, agreed.

Transcript edited for clarity.