Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: Biological-sex; Immunotherapy; Oncology; Quality-of-life; Systematic review; Targeted agents.
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.