Division of Medical Oncology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave., Room T2-058, Toronto, ON, Canada.
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
J Cancer Res Clin Oncol. 2023 Jul;149(8):4215-4224. doi: 10.1007/s00432-022-04270-0. Epub 2022 Sep 3.
The National Institutes of Health's policy for the inclusion of females in clinical research was a pivotal step towards the consideration of sex as a biological variable, which is of particular importance in oncology, given differential incidence and outcomes of cancer between the sexes, and known pharmacodynamic, pharmacokinetic, and immunological differences. Therefore, we aim to investigate if such biological sex-based differences translate to clinically meaningful outcome differences from recently approved systemic oncology therapies.
A systematic review of randomized control trials (RCTs) cited in Food and Drug Administration, European Medicines Agency, and Health Canada approvals was conducted. Chemotherapy, targeted agents, and immunotherapy RCTs reporting sex-based sub-group analyses for overall/progression-free survival (OS/PFS) were considered. Hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized. Sensitivity analyses for survival endpoints, drug type, and cancer site were conducted.
Ninety-nine RCTs were included, representing 62,384 patients (23,574 (38%) female). Pooled OS HRs [95% CIs] were 0.77 [0.72-0.81] and 0.76 [0.72-0.79] for females and males, respectively (P = 0.73), and 0.51 [0.47-0.56] and 0.57 [0.53-0.61] (P = 0.08) for PFS. Sensitivity analyses yielded similar results. No RCTs reported sex-based toxicity or quality-of-life (QOL) data.
Female and male patients appear to derive comparable benefits from recently approved systemic oncology therapies. Future RCTs are encouraged to report sex-based toxicity and QOL data.
美国国立卫生研究院关于将女性纳入临床研究的政策是将性别视为生物学变量的关键一步，这在肿瘤学中尤为重要，因为癌症在两性中的发病率和结果存在差异，并且已知存在药效学、药代动力学和免疫学差异。因此，我们旨在研究最近批准的系统肿瘤学治疗是否存在基于生物学性别差异的临床意义上的疗效差异。
对食品和药物管理局、欧洲药品管理局和加拿大卫生部批准的随机对照试验（RCT）进行了系统评价。考虑了报告总体/无进展生存率（OS/PFS）的基于性别亚组分析的化疗、靶向药物和免疫治疗 RCT。使用危险比（HRs）和 95%置信区间（CIs）。进行了生存终点、药物类型和癌症部位的敏感性分析。
共纳入 99 项 RCT，代表 62384 名患者（23574 名女性（38%））。女性和男性的 OS HRs [95% CIs] 分别为 0.77 [0.72-0.81] 和 0.76 [0.72-0.79]（P=0.73），PFS 分别为 0.51 [0.47-0.56] 和 0.57 [0.53-0.61]（P=0.08）。敏感性分析得出了类似的结果。没有 RCT 报告基于性别的毒性或生活质量（QOL）数据。
女性和男性患者似乎从最近批准的系统肿瘤学治疗中获得了相当的获益。鼓励未来的 RCT 报告基于性别的毒性和 QOL 数据。
