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Endometrial Cancer SGO 2025
Endometrial Cancer Landscape: Experts Review Latest Clinical Data From SGO 2025

Released: June 20, 2025

Expiration: December 19, 2025

Eloise Chapman-Davis
Eloise Chapman-Davis, MD, FACOG
Whitney S. Graybill
Whitney S. Graybill, MD, MS
Angeles Alvarez Secord
Angeles Alvarez Secord, MD, MHSc
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Key Takeaways
  • All patients with inadequate transvaginal ultrasound regardless of race should undergo timely endometrial biopsy to ensure early diagnosis.
  • Molecular subtyping is the standard of care in endometrial cancer; the modified ProMisE algorithm has unveiled nuanced prognostic implications for recurrence-free survival based on biomarkers associated with the poorest outcomes (ie, P53 and MMR status).
  • Various available immune checkpoint inhibitors (ie, durvalumab, dostarlimab, and pembrolizumab) in combination with standard of care chemotherapy have become the hallmark of first-line therapy for patients with advanced/recurrent endometrial cancer.

In this commentary, 3 clinical experts in the treatment of endometrial cancer (EC), Eloise Chapman-Davis, MD, FACOG; Angeles Alvarez Secord, MD, MHSc; and Whitney S. Graybill, MD, MS, share their thoughts and discuss recent changes in the therapeutic landscape of this disease including factors contributing to increasing incidence rates, delayed diagnosis, actionable molecular biomarkers, emerging clinical data, and answers to frequently asked questions from a live audience of healthcare professionals participating in a webinar on this topic.

Incidence of Endometrial Cancer and Factors Contributing to Health Disparities
Eloise Chapman-Davis, MD, FACOG:
Long-standing disparities in EC incidence and mortality may be attributed to stark racial inequalities, logistical barriers, and/or provider bias, among other factors related to a patient’s socioeconomic status and English proficiency, all of which are common hurdles in accessing proper care and potentially leading to delayed diagnosis.

The incidence of EC has increased approximately 6% since 2000 and is in part (~67%) attributed to more women being diagnosed with early-stage disease. Of note, non-Hispanic Black women have a 2-fold higher likelihood of dying from EC than non-Hispanic White women and are more likely to present with more advanced disease stages. The PUMBA study by Nolin and colleagues presented at the Society of Gynecologic Oncology (SGO) 2025 annual meeting illustrates real-world implications of disparities in endometrial sampling following transvaginal ultrasound (TVU). Although guideline-concordant care recommends timely (defined as ≤3 months) endometrial biopsy after an inadequate TVU or for a thick endometrium, Black women are much less likely to undergo biopsies despite having similar rates of abnormal TVU findings as non-Hispanic White women. This disparity is most likely compounded by the prevalence of fibroids in Black women, which often render TVUs inadequate and lead to workup delays. Thus, a universal and timely biopsy for all patients with postmenopausal bleeding—regardless of race—is needed to ensure early diagnosis.

A small qualitative study of 25 women ages 33-76 years, from the Southeast and Midwest region of the United States, and variable socioeconomic status, also presented at SGO 2025 revealed that a lack of trust and poor communication with care team, anxiety, and fear of a cancer diagnosis influence Black women’s willingness to undergo biopsies. The women in the study expressed a desire for more transparent communication about risks and benefits, personalized recommendations, and acknowledgment of medical racism. Trust-building, inclusive education, and shared decision-making emerged as critical tools in facilitating timely diagnosis.

Two additional studies, the Sister Study and the Black Women’s Health Study, investigated provocative links between the long-term use of chemical hair straighteners and relaxers and uterine cancer, but further studies are needed to confirm any association.

Current and Emerging Biomarkers for EC
Angeles Alvarez Secord, MD, MHSc:
There has been a rapid evolution in biomarker-driven treatment strategies focusing on the central role of molecular testing in personalized therapy. Two pivotal studies on molecular subtyping of cancer—The Cancer Genome Atlas study and the PORTEC-3 trial—revealed the significance of 4 biomarkers, namely, microsatellite instability (pMMR vs dMMR), POLE mutations, p53 status, and copy number (high vs low), that can be used to potentially predict a patient’s response to therapy and prognosis. For example, in PORTEC-3, patients with POLE-mutated EC experienced excellent recurrence-free survival, potentially enabling treatment de-escalation. The GOG-258 trial, which assessed the ability of a modified ProMisE algorithm to predict patient outcomes based on 3 molecular subtypes (p53wt, p53abn, and dMMR) was also pivotal in linking molecular subtypes to prognosis. Patients with p53-abnormal tumors had the worst prognosis, and those with p53 wild-type tumors benefited from combined chemoradiation vs chemotherapy (CT) alone based on data from the GOG-258 study. Poor outcomes in patients with serous and carcinosarcoma subtypes with HER2-altered status, highlights the important role of HER2-targeted agents like trastuzumab and trastuzumab deruxtecan.

The Endometrial Cancer Molecularly Targeted Therapy consortium findings were also presented at SGO 2025 and they show race-based molecular variations in biomarker signatures. For example, Black patients were more likely to have abnormal p53 expression and high HER2 expression and less likely to have dMMR status—potentially limiting their eligibility for immunotherapy options. The increased incidences of FGFR and BCL-2 mutations in Black women were also noted.

Results from retrospective analyses of the phase III GOG-249 trial, which aimed to assess whether molecular classification using MMR status and p53 expression can be used to predict survival benefits in patients with early-stage EC, showed that p53 expression is prognostic regarding recurrence-free survival and overall survival (OS) outcomes. Moreover, newer directions, such as use of baseline circulating tumor DNA status to assess prognosis and the benefits of combining an immune checkpoint inhibitor (ICI) with a PARP inhibitor, were investigated in the exploratory biomarker study from the phase III DUO-E/ENGOT-EN10 trial of durvalumab plus platinum-based chemotherapy followed by durvalumab maintenance with or without olaparib in patients with newly diagnosed advanced/recurrent EC. These new data represent exciting frontiers for personalizing cancer therapy in pMMR and in biomarker-agnostic situations.

Current Data and Emerging Results From SGO 2025
Whitney S. Graybill, MD, MS:
The evolving treatment landscape in EC can be summarized through 4 landmark phase III trials combining ICI with CT in advanced stage III/IV or recurrent EC: NRG GY018 (pembrolizumab plus CT), RUBY (dostarlimab plus CT), AtTEnd (atezolizumab plus CT), and DUO-E (durvalumab plus CT with or without olaparib). NRG GY018 demonstrated significantly improved progression-free survival (PFS) in patients with pMMR (13.1 vs 8.7 months; HR: 0.57) and those with dMMR (not reached vs 8.3 months; HR: 0.34). In addition, the NRG GY018 trial demonstrated preliminary OS improvement in patients with dMMR status (HR: 0.55), although data for OS remain immature for this study. These data led to FDA approval of pembrolizumab plus carboplatin and paclitaxel followed by pembrolizumab maintenance monotherapy for the treatment of adults with primary advanced or recurrent EC. The RUBY trial showed statistically significant improvements in 2-year PFS rates (dMMR: 61.4% vs 15.7%; pMMR: 28.4% vs 18.8%) and OS benefit in the overall population (44.6 vs 28.2 months with dostarlimab plus CT vs CT alone). These results led to the FDA approval of dostarlimab with carboplatin and paclitaxel, followed by dostarlimab maintenance monotherapy for the treatment of adults with primary advanced or recurrent EC. The AtTEnd trial of atezolizumab plus CT showed a significant improvement in PFS patients with advanced/recurrent EC with dMMR status (HR: 0.36; P = .0005) with interim analyses showing a positive trend in OS in favor of the atezolizumab-containing arm. The DUO-E trial also showed significantly improved PFS (dMMR: 31.8 vs not evaluable vs 7.0 months; pMMR: 15.0 vs 9.9 vs 9.7 months) and OS (median in intention-to treat population: not evaluable vs not evaluable vs 25.9 months) in favor of durvalumab plus CT with or without a PARP inhibitor vs CT alone, particularly if at least 1 molecular aberration present (eg, p53 mutation and PD-L1 expression).

Of note, durvalumab is approved by the FDA in combination with carboplatin and paclitaxel followed by durvalumab maintenance monotherapy only for patients with primary advanced or recurrent EC with dMMR status.

In summary, the available data for ICI plus CT demonstrated improved PFS and, in some cases, improved OS outcomes and particularly so in patients with dMMR status. Regarding safety, ICI added to CT has a manageable adverse event profile, albeit with increased immune-related adverse events (eg, arthralgia emerging years into treatment).

The SGO 2025 session closed with a presentation of long-term follow-up data from the randomized, double-blind, placebo-controlled phase III SIENDO trial of selinexor maintenance therapy following complete or partial response after ≥12 weeks of first-line taxane/carboplatin-based therapy for advanced or recurrent EC. Data presented at SGO 2025 showed selinexor prolonged median PFS (28.4 vs 5.2 months; HR: 0.44; P = .0005) in patients with p53 wild-type EC, regardless of MMR status (pMMR median PFS: 39.5 vs 4.9 months; HR: 0.36; P = .0011; dMMR median PFS: 13.1 vs 3.7 months; HR: 0.49; P = .0825).

Novel therapies on the horizon include tumor-infiltrating lymphocyte therapy (being investigated in the open-label phase II IOV-END-201 trial; NCT06481592) and next-generation antibody–drug conjugates like sacituzumab (phase II IMMU-132; NCT04251416) govitecan and sacituzumab tirumotecan (phase III TroFuse-005; NCT06132958). Panelists discussed the importance of continued biomarker testing to refine treatment and agreed on expanding clinical trial access and biomarker-guided therapy to optimize outcomes for all patients.

Frequently Asked Questions

What would you recommend to a patient with advanced or recurrent EC and pMMR status in the first-line setting?
Whitney S. Graybill, MD, MS:
At our center, we are offering ICI (either dostarlimab or pembrolizumab) in combination with CT if they have measurable stage III or IV advanced disease per current FDA indications.

Angeles Alvarez Secord, MD, MHSc:
I follow a similar approach. In the adjuvant setting, based on KEYNOTE-B21 data, I would look more closely for measurable stage III, positive sentinel node positivity, and dMMR status to make that determination.

What would you recommend in a patient with advanced disease and disease recurrence following first-line ICI plus CT?
Eloise Chapman-Davis, MD, FACOG:
Most people would turn to lenvatinib and pembrolizumab in patients with recurrent advanced disease in the second-line setting. However, there is concern and lack of empirical data in support of giving ICI in second-line after ICI plus CT in first line.

Angeles Alvarez Secord, MD, MHSc:
There is limited single-site experience for using lenvatinib in the second-line setting in patients who had progressed on pembrolizumab used in the first-line setting. In our consortium, we are exploring that but have not done this very often. I have personally tried lenvatinib in the second-line setting following progression on pembrolizumab plus CT in at least 1 patient, and she has done well so far. Another option might be considering available clinical studies evaluating antibody–drug conjugates (eg, trastuzumab deruxtecan; NCT04482309) or a trial of injectable trastuzumab plus pertuzumab (NRG-GY026; NCT05256225) if available.

Eloise Chapman-Davis, MD, FACOG:
I agree. You may also consider going back to the molecular profiling drawing board with patients progressing on ICI plus CT in the first-line setting. We are sending for HER2 status more often (as determined by gastric cancer criteria, with HER2-positive immunohistochemistry 3+ score defined by cytoplasmic membranous immunostaining that is incomplete and predominantly basolateral or membranous staining that is fully circumferential).

Are you using CT plus trastuzumab or ICI plus CT combination in patients with advanced disease and HER2-positive biomarker?
Angeles Alvarez Secord, MD, MHSc:
Most patients who are HER2 positive will also have p53-abnormal status and potentially also overlap with the pMMR group. For me, the greatest magnitude of benefit with ICI is seen in patients who have dMMR status. Because of this, I opt for CT plus trastuzumab. But without a direct head-to-head comparison we honestly do not know the answer to which combination is better (ICI plus CT vs trastuzumab plus CT) in this disease setting.

Your Thoughts
What are your thoughts on the current treatment landscape in patients with EC, including current health disparities, advances in prognostic biomarkers, available clinical data, or new directions?

Visit the program page to access the slides associated with this program and watch an on-demand webcast from the live event.

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