Minority Populations Largely Unrepresented in Gynecologic Cancer Clinical Trials

New research further revealed disparities in gynecologic cancer clinical trial enrollment, warranting increased efforts to improve representation in these trials.

The cohort study was published in JAMA Network Open and included 562,592 women who had endometrial or uterine, ovarian, or cervical cancer between 2004 and 2019, using data from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results Program (SEER).

Of the cohort, the vast majority (78.7%) of patients were White, with 10% Black, 6.8% Hispanic, 3.3% Asian, 0.3% American Indian/Alaska Native, and 1453 Native Hawaiian/Pacific Islander patients, and 3121 were classified as other race and ethnicity. The overall mean (SD) age at diagnosis was 62.9 (11.3) years.

With 548 of these women being enrolled in a gynecologic cancer clinical trial, this means less than 1% were represented, and this subset was largely comprised of White women (85.8%). A multivariable-adjusted model revealed that, compared with White women, clinical trial enrollment was lower among Asian (OR, 0.44; 95% CI, 0.25-0.78), Black (OR, 0.70; 95% CI, 0.50-0.99), and Hispanic (OR, 0.53; 95% CI, 0.33-0.83) women, who made up 2.2%, 7.1%, and 3.8% of the clinical trial subset, respectively.

These differences were not deemed significantly different for American Indian/Alaska Native women (OR, 1.37; 95% CI, 0.43-4.36), Native Hawaiian/Pacific Islander women (OR, 0.86; 95% CI, 0.12-6.16), or women of “other” race (OR, 0.48; 95% CI, 0.12-1.92), as the proportions of these women were more similar between the whole cohort and the clinical trial subset than for other races.

Interestingly, of the 3 included gynecologic cancer types, most women in the overall cohort had uterine cancer (58.6%), followed by ovarian (28.9%) and cervical (12.6%) cancer. However, the vast majority of women in clinical trials had ovarian cancer (78.3%), followed by uterine (12.2%) then cervical (9.5%) cancer.

According to the authors, they found intriguing patterns after analyses comparing the race-specific clinical trial enrollment prevalence within the NCDB sample with the corresponding race-specific cancer prevalence in the broader US population with gynecologic cancer. Participation-to-prevalence ratios (PPRs) were computed by dividing the percentage of clinical trial participants specific to each race and ethnicity in the study sample by the corresponding percentage of those racial and ethnic groups in the SEER database. Compared with the US population, White women were adequately or overrepresented for all 3 cancer types (PPRs ≥ 1.1), and Black women were adequately or overrepresented for endometrial and cervical cancers (PPRs ≥ 1.1) but underrepresented for ovarian cancer (PPR ≤ 0.6). Meanwhile, Asian and Hispanic women were underrepresented among all 3 cancer types (PPRs ≤ 0.6).

“Together, these analyses provide novel information on the landscape of racial and ethnic disparities in gynecologic cancer treatment,” the authors said.

Disparities in gynecologic oncology between Black and White populations specifically have been extensively studied, but research on other racial and ethnic groups is limited. The current study revealed that Asian and Hispanic women are underrepresented and have lower odds of clinical trial enrollment compared with White women, aligning with previous research indicating lower enrollment of women from these groups in precision oncology and cervical cancer clinical trials. Additionally, a review of trials sponsored by the National Cancer Institute found that Hispanic women—but not Asian women—were less likely to be enrolled in ovarian, uterine, or cervical cancer clinical trials. Due to the small number of patients from Native Hawaiian/Pacific Islander, American Indian/Alaska Native, and other racial groups, meaningful estimates for clinical trial enrollment odds or PPRs could not be provided.

Besides race and ethnicity, clinical trial enrollment was influenced by other factors, including the presence of comorbidities, which correlated with decreased odds of participation—again consistent with previous research. Traditionally, clinical trials have excluded individuals with medical comorbidities for safety reasons. However, in 2017 and 2021, the American Society for Clinical Oncology recommended widening eligibility criteria to enhance generalizability. Other factors associated with lower clinical trial enrollment included older age; residence in zip codes with higher income and lower educational attainment; living in urban, small, or medium-sized counties; and receiving treatment in the South, Midwest, or Pacific regions, compared with the Northeast. On the other hand, treatment at an academic or research program or an integrated network cancer program was linked to higher odds of clinical trial participation.

“Most of these associations were expected on the basis of prior literature; however, our finding that women living in areas with higher area-level income were less likely to participate in clinical trials was surprising,” the authors said. “It is likely that area-level income also captures unmeasured neighborhood effects underlying this unexpected association. Future studies that also include individual-level income measures will be useful in contextualizing this association.”

The study’s limitations stem from the available data in the NCDB, which lacks crucial information on patient and oncologic characteristics, trial specifics, and contextual information on therapeutic areas. Unmeasured confounding is also a possibility, and the absence of details on the pathway to clinical trial enrollment for different racial and ethnic groups hindered the authors’ ability to recommend specific interventions. Additionally, the exclusion of approximately 45% of the original sample due to missing values in key variables may have led to imprecise estimates, particularly for American Indian/Alaska Native and Native Hawaiian/Pacific Islander women, highlighting the need for future studies to address these disparities.

“Further work aimed at understanding the race-specific barriers and facilitators that impact enrollment of gynecologic oncology patients in clinical trials is imperative,” the authors concluded. “Although we noted lower clinical trial enrollment in multiple minoritized groups, the pathways leading to these outcomes are likely diverse and will require targeted interventions.”