A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.

In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.

“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology 2024 Annual Meeting on Women’s Cancer on March 17, 2024.

Importantly, Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.

Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Kopelman told attendees.

Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.

Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Kopelman explained.

Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.

All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.

Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.

When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).

In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).

When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Kopelman noted.

Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).

Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.

One caveat, said Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which “offers a potential attractive therapeutic opportunity.”

The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Kopelman.

The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.

David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”

“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.

The study had no commercial funding. Kopelman, O’Malley, and AlHilli had no relevant disclosures.

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