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Do female and male patients derive similar benefits from approved systemic oncology therapies? A systematic review and meta-analysis

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Abstract

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.

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Data availability

All data generated or analysed during this study are included in this published article and its supplementary information files.

Abbreviations

RCT:

Randomized control trial

FDA:

Food and Drug Administration

EMA:

European medicines agency

HC:

Health Canada

PFS:

Progression-free survival

TTP:

Time to progression

RFS:

Recurrence-free survival

OS:

Overall survival

HR:

Hazard ratio

CI:

Confidence interval

QOL:

Quality-of-life

CTLA-4:

Cytotoxic T-cell antigen-4

PD-1/PD-L1:

Programmed death-1/programmed death ligand-1

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Acknowledgements

The Canadian Centre for Applied Research in Cancer Control (ARCC) is funded by the Canadian Cancer Society Research Institute grant #2015-703549. We also acknowledge the contributions of Mahin Qureshi and Sierra Cheng, in study design and data extraction.

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Author notes

  1. Vanessa Arciero and Erica McDonald contributed equally to this work.

Authors and Affiliations

  1. Division of Medical Oncology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave., Room T2-058, Toronto, ON, Canada

    Vanessa Arciero, Erica McDonald, Vivian Nguyen, Ronak Saluja, Michael Raphael, Ambica Parmar & Kelvin K. W. Chan

  2. Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Kelvin K. W. Chan

  3. Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada

    Kelvin K. W. Chan

Authors
  1. Vanessa Arciero
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  2. Erica McDonald
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  3. Vivian Nguyen
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  4. Ronak Saluja
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  5. Michael Raphael
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All named authors have made substantial contributions to the development of this manuscript, and have read and approved the final version.

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Correspondence to Kelvin K. W. Chan.

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Arciero, V., McDonald, E., Nguyen, V. et al. Do female and male patients derive similar benefits from approved systemic oncology therapies? A systematic review and meta-analysis. J Cancer Res Clin Oncol 149, 4215–4224 (2023). https://doi.org/10.1007/s00432-022-04270-0

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