Association Between Sex and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta Analysis

Abstract

Aim: To explore the association between sex and immune checkpoint inhibitors (ICIs). Materials & methods: We assessed the difference in survival outcomes from ICIs between sexes using an interaction test. Results: 108 studies representing 70,243 patients were included. In the first-line setting, the pooled interaction HR was 0.97 (95% CI: 0.91–1.04). In the subsequent-line setting, the pooled interaction HR was 0.85 (95% CI: 0.77–0.95). When ICIs were given as perioperative therapy or as systemic therapy in patients with positive PD-L1 expression, both men and women obtained equal survival benefits. Conclusion: Both sex, line of therapy, cancer (sub)type and PD-L1 status should be taken into account in the assessment of risk versus benefit when deciding to offer ICIs to patients.

Plain language summary

There are many differences between men and women, and whether these differences also affect the efficacy of immune checkpoint inhibitors is important because immune checkpoint inhibitors have been widely accepted as standardized treatments for patients with malignant tumors. Previous studies have reported conflicting results. This research was conducted to reassess this sex disparity with additional available reports. We found that both men and women can benefit from immune checkpoint inhibitors, while sex should be taken into account when deciding to offer immune checkpoint inhibitors to patients who have already been heavily treated.

Keywords: :

• anticancer immunity
• cancer
• immune checkpoint inhibitors
• immune therapy
• meta-analysis
• randomized controlled trials
• sex
• sex disparity
• survival
• treatment outcome

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/imt-2023-0307

Author contributions

J Li developed the idea for the study (conceptualization). J Li was responsible for funding acquisition and resources. All authors designed the study, collected the data, performed the statistical analysis, analyzed and interpreted the data and wrote and reviewed the manuscript and approved the final version.

Acknowledgments

The authors thank all participants and investigators of the included trials.

Financial disclosure

This work is supported in part by the Medical Research Project of The Third Hospital of Mianyang (202222). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

As no direct human subjects were involved in this review, institutional review board approval was not needed.

Data sharing statement

This systematic review and meta-analysis used data from published studies; data are available from these individual published studies.