Khan Maheen H, Ibanez Kristen R, Bowen Courtney, Donohue Duncan, Oluloro Ann, Swisher Elizabeth M, Lee Jung-Min
Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
JCO Glob Oncol. 2025 May;11:e2400636. doi: 10.1200/GO-24-00636. Epub 2025 May 29.
To evaluate the impact of international enrollment in landmark gynecologic cancer (Gyn-Ca) trials that supported the US Food and Drug Administration (FDA) drug approvals.
We examined the FDA drug approval database for approved Gyn-Ca agents between January 2014 and June 2024. We then extracted clinical trial identifiers supporting these approvals using FDA safety labels. Expected enrollment was calculated using gynecologic disease site incidence data from the US Cancer Statistics Program and compared with actual trial enrollment reported on ClinicalTrials.gov.
From 2014 to 2024, 30 Gyn-Ca trials supporting 28 FDA approvals were conducted in US/international (86.7%), international-only (10%), and US-only sites (3.3%) and enrolled 15,294 patients, with 14,053 remaining (74.0% White, 4.1% Black, 12.7% Asian, 8.7% other) after screening for trials not reporting race. Black (-11.0%; < .0001), Hispanic/Latino (-3.5%; < .0001), and elderly (-12.6%; < .0001) participants were under-represented, whereas Asians (+6.8%; < .0001) were over-represented. Asian (18.3% 3.5% in trials with or without East Asian sites; odds ratio [OR], 6.19 [95% CI, 5.29 to 7.25]; < .0001) and Hispanic/Latino (18.6% 4.6% in trials with or without South American sites; OR, 4.75 [95% CI, 4.00 to 5.63]; < .0001) enrollment was higher in trials that included East Asian and South American sites, respectively. Black enrollment did not improve despite trials including recruitment in Africa (3.2% 4.1% Black enrollment in trials with or without African sites; OR, 0.83 [95% CI, 0.38 to 1.83]; = .53).
Black, Hispanic/Latino, and elderly patients were under-represented in pivotal Gyn-Ca trials, whereas Asian patients were over-represented, compared with expected enrollment proportions. Postmarketing studies on under-represented groups should be considered to assess drug efficacy and safety in these populations.
评估国际参与支持美国食品药品监督管理局（FDA）药物批准的标志性妇科癌症（Gyn-Ca）试验的影响。
我们查阅了FDA药物批准数据库，以获取2014年1月至2024年6月期间批准的Gyn-Ca药物。然后，我们使用FDA安全标签提取支持这些批准的临床试验标识符。使用美国癌症统计计划的妇科疾病部位发病率数据计算预期入组人数，并与ClinicalTrials.gov上报告的实际试验入组人数进行比较。
2014年至2024年期间，在美国/国际（86.7%）、仅国际（10%）和仅美国（3.3%）的地点进行了30项支持28项FDA批准的Gyn-Ca试验，共招募了15294名患者，在筛选未报告种族的试验后，还剩下14053名（74.0%为白人，4.1%为黑人，12.7%为亚洲人，8.7%为其他种族）。黑人（-11.0%；P<0.0001）、西班牙裔/拉丁裔（-3.5%；P<0.0001）和老年患者（-12.6%；P<0.0001）的代表性不足，而亚洲人（+6.8%；P<0.0001）的代表性过高。在有或没有东亚地区的试验中，亚洲人入组率为18.3%±3.5%；优势比（OR）为6.19[95%置信区间（CI），5.29至7.25]；P<0.0001），在有或没有南美地区的试验中，西班牙裔/拉丁裔入组率为18.6%±4.6%；OR为4.75[95%CI，4.00至5.63]；P<0.0001），分别在包括东亚和南美地区的试验中更高。尽管试验包括在非洲招募患者，但黑人入组率并未提高（在有或没有非洲地区的试验中，黑人入组率为3.2%±4.1%；OR为0.83[95%CI，0.38至1.83]；P=0.53）。
与预期入组比例相比，在关键的Gyn-Ca试验中，黑人、西班牙裔/拉丁裔和老年患者的代表性不足，而亚洲患者的代表性过高。应考虑对代表性不足的群体进行上市后研究，以评估这些人群中药物的疗效和安全性。
