Racial representation in multicenter clinical trials leading to drug approvals for gynecological cancer indications by the US Food and Drug Administration (FDA).

66 Background: Enrollment disparities in gynecologic (Gyn) cancer clinical trials in the United States (US) are well-documented. However, there is limited data evaluating how recruitment sites in international clinical trials contribute to racial representation, specifically in Gyn cancers. Here, we examined racial enrollment and geographic location in clinical trials that have led to approval for Gyn cancer applications. Methods: Agents approved by the FDA for Gyn cancer treatment and corresponding clinical trials were identified from the FDA Drug Approvals and Databases. Enrollment data were abstracted from ClinicalTrials.gov then cross-checked with published manuscripts and FDA labels. Using Gyn disease site prevalence from the 2021 SEER database, we calculated expected enrollment proportions by race and compared these to actual clinical trial enrollment data. The binomial test was used to compare expected vs. observed proportions with White patients as the reference group. Results: From 2014 to 2024, 9 drugs received 22 FDA approvals for ovarian (n=13), endometrial (n=4), or cervical cancer (n=5). These approvals were based on 28 clinical trials enrolling a total of 13,763 patients (75.7% White, 3.4% Black, 12.0% Asian, 8.9% Other/Unknown). These trials included 1 (3.6%) US only study, 3 (10.7%) non-US, primarily Europe-based studies (PAOLA-1, AURELIA, STUDY42 Europe + Australia), and 24 (85.7%) international studies across the US and 46 other countries. Considering the distribution of race (White: 86.3%, Black: 8.4%, Asian: 4.9%) of Gyn cancers in the US, Black patients had lower enrollment (45% of expected enrollment) vs. White patients (95% of expected enrollment, P<0.0001). African countries were rarely included among the recruitment sites. Two international trials reported patient recruitment from South Africa (3.2% Black, 6/188 patients, 38% of expected enrollment).However, Asian patients had higher enrollment (269% of expected enrollment, P<0.0001) compared to White patients. In 13 trials that included study sites in East Asia, Asian patients comprised 16% of the trial population (1310/8205 patients; 327% of expected enrollment) vs. 3.2% in trials that did not open in Asia (n=15) (181/5558 patients; 67% of expected enrollment). Conclusions: Black patients were underrepresented in pivotal trials that led to FDA approvals for Gyn cancers. Overrepresentation of Asian patients was likely due to international enrollment from East Asia. Post-marketing retrospective studies or additional studies focused on underrepresented groups are needed to assess true drug efficacy and safety in US populations that are disproportionately affected by Gyn cancer mortality.