Spotlighting Disease Prevention Efforts Alongside Treatment Breakthroughs Is Crucial for Endometrial Cancer Risk Reduction

The integration of immunotherapy with standard chemotherapy regimens has established a new and effective standard of care regimen for patients with advanced or recurrent endometrial cancer, according to Brian Slomovitz, MD. Although these treatment advancements are important to communicate, it is critical to increase awareness of next steps for improving patient outcomes and disease prevention efforts in the field of gynecologic oncology, he said.

“Part of our job as clinicians who treat this disease is not only to come up with the best treatment options but to help educate our patients and our colleagues about better ways to treat cancer and even better ways to prevent it,” Slomovitz shared in an interview with OncLive® during Gynecologic Cancer Awareness Month, which is marked in September. “It is really an exciting time [in gynecologic cancer research], especially regarding [disease] prevention.”

In the interview, Slomovitz discussed the benefits seen with chemoimmunotherapy combinations for patients with recurrent or advanced endometrial cancer regardless of mismatch repair (MMR) status; the essential role of universal biomarker testing to guide personalized treatment decisions in recurrent disease; and the importance of educating patients about how weight impacts the risk of endometrial cancer.

Slomovitz is the director of gynecologic oncology and cochair of the Cancer Research Committee at Mount Sinai Medical Center, and a professor of obstetrics and gynecology at Florida International University in Miami.

OncLive: What is your typical treatment decision-making process for recurrent endometrial cancer, and what factors influence this choice?

Slomovitz: There are a lot of new treatment options for patients with recurrent or advanced endometrial cancer. One of them, and foremost, is incorporating immunotherapy with chemotherapy in the management of the disease. We found that for all endometrial cancer patients, regardless of the biomarker profiling, there is a benefit [with this approach]. Patients with MMR-deficient tumors are [generally] much more responsive to immunotherapy. However, even those tumors with MMR-proficient [tumors] do respond well when adding immunotherapy to traditional chemotherapy.

We also look at other factors. For example, we consider whether patients may benefit from hormonal therapy, or if other biomarkers that are overexpressed in the tumors—for example, HER2—as a means of potential targets that we can exploit.

In which scenarios would you incorporate immunotherapy into a chemotherapy regimen?

When we talk about what type of treatment we are going to use for recurrent cancers, the backbone in the past has always been carboplatin and paclitaxel. Now, we are really doing, or at least educating [other about], universal biomarker testing. That biomarker testing will help delineate the MMR status—is it deficient or proficient? This is also similar to microsatellite instability or stability and other markers that we are looking at. For most patients, unless they have another contraindication, we would consider using that treatment.

What pivotal findings from part 1 of the phase 3 RUBY trial (NCT03981796) supported the FDA approval of dostarlimab plus chemotherapy for the "all-comer" population of patients with primary advanced or recurrent endometrial cancer?

Part 1 of RUBY is a study [evaluating] chemotherapy plus or minus dostarlimab-gxly [Jemperli] in women with advanced or recurrent endometrial cancer in the first-line setting.1,2 It [randomly assigned] patients to receive either dostarlimab [(n =245) or placebo (n = 249)] with their chemotherapy. Those patients who received dostarlimab experienced improved progression-free survival in the "all-comer" population [vs chemotherapy alone. (HR, 0.64; 95% CI, 0.51-0.80; 1-sided P < .0001)]. [There were] also suggestions of an overall survival benefit [with dostarlimab plus chemotherapy] in all populations [HR, 0.69; 95% CI, 0.54-0.89; 1-sided P = .002].

We now have more prolonged data in this setting that reconfirms the earlier findings. The farther out we go, we are still seeing that benefit. The data are really more mature for the RUBY than some of the other studies [in this space].

How has this expanded approval affected your practice? Are there any particular benefits or challenges associated with using dostarlimab in this broader patient population?

In general, based on the data from RUBY, the phase 3 NRG-GY018 (NCT03914612), and even the phase 3 DUO-E trial (NCT04269200), we know that immunotherapy plays a role in the management of this disease. I use several different regimens in my practice. The RUBY trial, in particular, allowed [patients with] carcinosarcomas [to enroll], where the other studies didn't necessarily allow for that. There was also a subpopulation of patients who are going to be treated in what we call the adjuvant setting, which was nicely included in the RUBY trial. This makes it stand out.

I am currently using dostarlimab in combination with chemotherapy for my patients with disease, amongst other regimens. I am also a clinical trialist. Not only are we looking to see what the next greatest therapies are, but we need to compare them with the current best therapies. With all these advances, we moved immunotherapy and chemotherapy into the control arm of the studies that are ongoing now and that we are writing now, because it is [clear] that this is the best [available] therapy [that new regimens should be compared against]. Now we need to do better than that.

What are some ongoing trials or emerging agents of interest in the field of gynecologic oncology?

We are excited for the upcoming [2025] ESMO [Congress] in Berlin, as well as the IGCS 2025 Annual Global Meeting in Gynecologic Oncology this November. We are anticipating a lot of good data [to emerge from those meetings. We are looking at more ways to [leverage] immunotherapy, not just in endometrial cancer, but in ovarian cancer as well.

There are also going to be some data presented at these meetings [with] non-chemotherapy, non-immunotherapy [options] for treating this disease. We are excited to hear about some of the latest data that are going to come out in that setting.

What is the importance of recognizing Gynecologic Cancer and Endometrial Cancer Awareness Month?

Gynecologic Cancer Awareness Month is a great time for us to get out there and talk about the cancer, talk about what the next steps are to get better outcomes for our patients, [discuss] what the next steps are with the standard of care, and [outline] where we are going with some of our research.

But we can't talk about treatment without [discussing] prevention. We need to educate our patients about obesity. A recent article that came out [showing whether] weight loss with the GLP-1 [glucagon-Like peptide-1] medications, like semaglutide [Ozempic] can decrease the risk of endometrial cancer. We could talk about the next, latest, and greatest therapies, which is always exciting, but [it would be even better] if we could prevent [this disease]. Reassuring ourselves that weight loss could help prevent cancer—these are the things that we love to talk about during this month, not just the new immunotherapies or the latest surgery that we are doing.

References

1. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA. August 1, 2024. Accessed August 23, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy
2. Ryan C. FDA approves expanded indication for dostarlimab plus chemo in primary advanced or recurrent endometrial cancer. OncLive. August 1, 2024. Accessed September 22, 2025. https://www.onclive.com/view/fda-approves-expanded-indication-for-dostarlimab-plus-chemo-in-primary-advanced-or-recurrent-endometrial-cancer