Drs Kathleen Moore and David O’Malley share their perspectives on the incidence and prognosis of mEC, including mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) disease, and then review a scenario of a patient with dMMR mEC who was treated with first-line carboplatin/paclitaxel.
Kathleen Moore, MD: Hello, and welcome to this OncLive® Insights program on “My Treatment Approach: Metastatic Endometrial Cancer.” I’m Dr Kathleen Moore, the Virginia Kerley Cade endowed chair in cancer development and professor of gynecologic oncology at the Stephenson Cancer Center in Oklahoma City. I’m pleased to discuss how we approach a patient with metastatic endometrial cancer with my colleague and friend Dr David O’Malley, a gynecologic oncologist and professor in the department of obstetrics and gynecology at The Ohio State University College of Medicine and the director of the division of gynecologic oncology at the James Cancer Center. Let’s get started.
Why are we talking about endometrial cancer today? Well, hopefully you know this, but just in case you don’t, endometrial cancer is the only solid tumor increasing in both prevalence and mortality, so we have a big challenge in front of us in terms of preventing this, grappling with this disease, and finding more effective therapies. We are learning a tremendous amount about endometrial cancer and the different subtypes. It is not just 1 disease just because it all starts in the uterus. There are very distinct subsets that are being increasingly identified that have particular therapies that may or may not be appropriate. We’re going to talk to you about that today.
One of the more tangible subgroups or biomarkers that we are being able to bring into our treatment decisions is the presence or absence of mismatch repair deficiency. We also look for microsatellite instability, microsatellite high or microsatellite stable. These 2 biomarkers are already actionable, and we’ll talk about that. It affects about 30% of cases of endometrial cancer at baseline. About 30% are found to be deficient in mismatch repair proteins or microsatellite high.
At this point, the prognostic significance of identifying that is a little unstable in terms of opinions. Overall, it seems to not have a prognostic significance, although some studies would suggest perhaps [patients] do a little bit better. It may be more predictive in terms of response to chemotherapy in some settings, although even that has not been as definitively established, but it certainly is predictive in terms of response or lack thereof to immune checkpoint inhibitors. So we’ll talk about that today. We’re going to talk through treatment strategies, and we’re going to do this by highlighting a case.
This is a very typical case, this is a 67-year-old woman. She’s postmenopausal. She presented with intermittent vaginal bleeding, which is how endometrial cancer presents. She also had other symptoms though, increased urinary frequency and some cramping that went along with this bleeding. She’d been menopausal for about 13 years and is widowed. Upon physical exam she has overall an excellent performance status, but is a little tender over her uterus. She underwent endometrial biopsy, which would be the standard of care for a postmenopausal patient who presents with bleeding. This was appropriately done and revealed an endometrioid endometrial adenocarcinoma that was grade 3, or poorly differentiated. That biopsy was sent for mismatch repair deficiency [testing]. Sometimes you do it on the biopsy and sometimes you wait until the hysterectomy. Hers was sent for mismatch repair when she was found to be deficient.
Once this diagnosis came back, because she was grade 3 and she had tenderness, there was concern that potentially she had metastatic disease. So she underwent a CT scan of the chest, abdomen, and pelvis and was found to have not only a mass within her uterus, but also it appeared to be extending into her bladder. Her particular provider obtained a CA-125 [cancer antigen 125 test], which was a little elevated at 41 U/mL. This was in June of 2022, and within a month she was started on carboplatin and paclitaxel, which has been well tolerated to date, and she’s going to complete 6 planned cycles, and then assess her response and follow-up from there. This is sort of the beginning of her story. She has stage IVA, grade 3 endometrioid endometrial cancer.
Transcript edited for clarity.