First-Line Therapy for dMMR mEC: Patient Conversations and Treatment Goals


Comprehensive discussion on patient counseling, and treatment goals, and expectations for those beginning first-line chemotherapy for dMMR metastatic endometrial cancer.


Kathleen Moore, MD: We’ll return to the patient. With this patient, you’re treating her with frontline chemotherapy, she has metastatic disease; how do you counsel her in terms of expectations? What’s the likelihood that she’s going to respond or get to a complete response [CR]? Is she really going to get 6 cycles and stop, or do you treat indefinitely? How do you counsel her as to what her expectations are for this line of therapy?

David O’Malley, MD: It’s such a challenge because in the past we just treated until the patients begged us to stop. We have kind of gone away from that, both in cervix and uterine cancer, and more we try to give them a break after 6 and up to 8 cycles. I think, as we look at these patients, that would be one of the first questions I would ask, is she curable? Is her disease localized to the pelvis? Do we still have a chance of curative intent? There are so few data on stage IVA. Is there as high as a 20% curative intent? Maybe it’s that high, maybe it’s only 10%. If you can get that disease down, and as you said, remove the primary disease plus or minus radiation, if they’re a surgical candidate, that’s the best option. When we look at these options in the patients, if I think she’s curable, I’m going to counsel her one way. If I don’t think she’s curable, in that scenario, I have the conversation that a response with chemotherapy is probably about 55%, plus or minus 5% or so. When we look at that, and how long and what percentage get complete responses, most do not get complete responses, especially if they have bulky disease. That’s why Dr Moore and I talked about trying to improve that local control of it with surgery or potentially radiation. So that’s the first thing, do I think she’s curable? If she’s not curable, I’d set the expectation that our goal here is to control disease.

Kathleen Moore, MD: This patient is mismatch repair deficient and she missed the window for NRG-GY018. [That study is] led by our good friend, Ramez Eskander, [MD,] from UCSD [University of California, San Diego]. And [the patient] doesn’t have the Merck study [GOG-3064] open at her site. You know she’s mismatch repair deficient, so are you adding it [pembrolizumab] in the front line off-label at this point, or are you waiting?

David O’Malley, MD: I’m not. It’s a great question. I get that question all the time. I’m not, but I would in this particular patient, treat with chemotherapy, and if they had persistent disease, they meet the indication for pembrolizumab or dostarlimab. Both of those agents could be used if they have persistent disease after optimizing chemotherapy. I’d probably only treat them for 6 cycles. If their disease was still regressing, I’d may go out to 8. I have found I can’t get much more than 8 cycles of platinum in before the patients start having bone marrow suppression, hypersensitivity, and chronic fatigue. So if they had persistent disease after 6 cycles, I would then add dostarlimab or pembrolizumab at that point.

Kathleen Moore, MD: And how long would you continue that, indefinitely? This is someone who is potentially curative, but maybe not.

David O’Malley, MD: We debate this; the trials are 2 years. Almost all the trials are 2 years. I’ve been sticking with that, particularly if they have a complete response or if they just have a small lymph node. At the core, as an oncologist, I still say, “Are you kidding me? I’m going to stop a therapy just giving them 2 years?” I have tended to stop it at that 2 years, watch them closely, usually do scans every 3 months, and then reintroduce the IO [immuno-oncology] if they start to show progression. I can tell you, when I’ve had the opportunity to stop, in uterine cancer, I don’t know if I’ve had to restart. In cervix cancer, I’ve had to restart.

Kathleen Moore, MD: That’s another area where I think melanoma is way ahead of us, and in these sort of retreatments we need to catch up a bit to know how best to take care of these patients. It’s a bit of a data-free zone that may kind of harm patients because we may hold them on it for longer than they need it, just based on our own discomfort with discontinuation of something that’s working.

David O’Malley, MD: You’re treating the oncologist, rather than the patient.What do you do, Dr Moore? Are you stopping at 2 years if she has persistent disease vs CR?

Kathleen Moore, MD: If I have someone who is in a CR, I do stop at 2 years. I think if I have known disease that’s being held stable, I get a little uncomfortable and I do have a conversation with the patient about it. Just to add a little more voodoo onto it, I do follow in these patients, I send the BESPOKE ctDNA [circulating tumor DNA] test for minimal residual disease, and I watch that as well. Sometimes it’s interesting with immunotherapy, you think you’re following disease, and they had ctDNA that could be measured and then it’s gone, but you still see these nodes or something on the imaging, and they have no circulating tumor DNA. So I don’t know if it correlates it or not, but it makes me feel a little better about stopping it when the patient wants to stop. All of what I just said is completely data free, no data.

David O’Malley, MD: No. And I think as we look at this and say, that anxiety of that thickening, right? This patient would continue to have thickening in their bladder. Do you do a cystoscope to look and see if they have persistent disease? The uterus is not going away, so she’s going to have disease. This is a case that if she did get that complete response, then I would definitely do a hysterectomy at that point. Get that disease out and make sure she doesn’t have persistent disease, if you can, and you can get in the planes without requiring a major bladder resection.

Kathleen Moore, MD: Yes,I really love getting the primary tumor out.

Transcript edited for clarity.

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