Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio, USA.
Department of Medicine, Greater Baltimore Medical Center, Baltimore, Maryland, USA.
Int J Cancer. 2024 Dec 1;155(11):1958-1968. doi: 10.1002/ijc.35110. Epub 2024 Aug 19.
Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.
当代癌症治疗方法在男性和女性中的疗效和副作用往往不同。然而，支持当代抗癌药物的关键试验中是否有足够的女性参与尚不清楚。利用 Drugs@FDA 数据库、clinicaltrials.gov、MEDLINE 和公开的 FDA 药物审查，我们确定了所有支持 FDA 批准抗癌药物的关键（二期和三期）非性别特异性试验（1998-2018 年）。观察到的入组率与同期美国国家癌症研究所监测、流行病学和最终结果（SEER）报告率和美国人口普查数据库得出的预期人群率进行了比较。主要结果是根据癌症类型，通过参与与流行率的比值（PPR）来评估试验中女性的比例代表性。次要结果是报告任何与疗效和/或安全性相关的性别特异性分析，而不论治疗组如何。总体而言，有 148 项试验，纳入了 60216 名参与者（60.5±4.0 岁，40.7%为女性，79.1%为生物、靶向或免疫治疗），评估了 99 种药物。146 项试验（98.6%）报告了性别，其中 40.7%（24538 人）为女性，而男性为 59.3%（35678 人）（p<.01）。总的来说，与相应疾病类型的癌症发病率相比，女性在 66.9%的试验中代表性不足；平均权重 PPR 为 0.91（相对差异：-9.1%，p<.01）。女性在胃癌（PPR=0.63）、肝癌（PPR=0.71）和肺癌（PPR=0.81）试验中代表性不足的情况最为严重。4.0%的试验报告了基于性别的安全性数据。女性充分入组与药物疗效之间没有关联（HR：0.616 与 0.613，p=0.96）。随着时间的推移，女性被招募进入临床试验的比例没有差异。在支持当代 FDA 批准的癌症药物的关键临床试验中，女性通常代表性不足，并且通常不报告与疗效和安全性相关的性别特异性结果。
