Gini F. Fleming, MD: Hi, I’m Dr. Fleming. I’m a medical oncologist specializing in the treatment of GYN malignancies at the University of Chicago.
OBR: What findings related to immunotherapy in endometrial cancer do you think are most likely to change practice?
Dr. Fleming: Well, I think we already have immunotherapy approved for the treatment of recurrent microsatellite instable disease after prior chemotherapy. However, the two trials that we heard updates of at this meeting show an incredibly dramatic benefit in progression-free survival. And although the results are early, likely a significant large benefit in overall survival for using immunotherapy upfront, in combination with chemotherapy, for women with metastatic or recurrent endometrial cancer whose disease is microsatellite instable.
It was more surprising to me, but also very nice, that there was also benefit, although it was smaller, for women whose tumors were microsatellite stable. And I think that the future is going to be that it will be standard for all women with metastatic endometrial cancer to have immunotherapy plus chemotherapy, at least until we figure out some predictive markers that might tell us who are the few who won’t benefit.
OBR: What testing is currently used when considering immunotherapy?
Dr. Fleming: It is standard of care that all patients with endometrial cancer have mismatch repair (MMR)-deficiency testing done at the time of diagnosis with early-stage disease as screening for Lynch syndrome. This information gives you also what you need to know, since the vast majority of patients with mismatch repair-deficient tumors will have microsatellite instable tumors.
OBR: Have any recent data surprised you?
Dr. Fleming: Again, I was surprised at the magnitude of benefit for the addition of immunotherapy to chemotherapy for women with microsatellite stable disease. To me, that was unexpected and very nice.
OBR: What advice would you give regarding patient selection and other considerations when it comes to adding immunotherapy to chemotherapy?
Dr. Fleming: The question is about whether or not there are patients who ought to be selected or not selected for the addition of immunotherapy upfront. Most oncologists are very familiar with using immunotherapy in other diseases, and the same caveats apply to endometrial cancer, that women with active autoimmune diseases are at substantial risk for complications.
OBR: Which upcoming research are you most closely watching?
Dr. Fleming, MD: I’m very much looking forward tomorrow morning to the results of the DESTINY-PanTumor02 trial, which is an umbrella trial of the antibody drug conjugate trastuzumab deruxtecan. It’s an umbrella trial that is aimed at HER2-positive tumors across the spectrum of malignancies. However, there is, as of now, no anti-HER2 therapy approved for endometrial cancer, despite the fact that at least 5% of our worst endometrial cancers, the serous, will be HER2-amplified, and a higher percentage will be low-level immunohistochemistry (IHC)-positive or have a HER2 mutation. I am incredibly excited to see the results of this antibody-drug conjugate in this population. I think it could be a huge stride forward.
I’m also very interested to see trials in metastatic disease of single-agent upfront immunotherapy. It would obviously be nicer for all of us and for our patients, most especially, if we didn’t have to use the chemotherapy at all in some subgroups of treatment.
There [are] also several trials of using immunotherapy in the adjuvant setting, as it would be nicer yet if people never got metastatic disease. I think it’s a very, very exciting time for endometrial cancer and there’s a lot of results to look forward to.
OBR: What else should oncologists know about recent news or changes affecting endometrial care?
Dr. Fleming: I think that there’s going to be a change in the staging system for endometrial cancer, whereby the POLE mutation is incorporated into stage. As you know in the TCGA analysis, POLE-mutated tumors, although they may well be high-grade, when they’re early stage, have an incredibly good prognosis and probably don’t need any further therapy at all. However, this testing has to be done by next-generation sequencing, and up to this point, has not been standard or necessarily approved by insurance companies.
I think as POLE mutations have more implications for our practice, and as they become part of the staging system, I expect that insurance will start to cover next-generation sequencing universally. And this will be a huge step forward in personalizing the treatment for our patients and avoiding toxicity in some who really don’t need it.
This transcript has been lightly edited for clarity.
