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Review
. 2024 Jan 16;16(2):382.
doi: 10.3390/cancers16020382.

The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

Xingyu Zhong  1 , Jianxuan Sun  1 , Na Zeng  1 , Yifan Xiong  1 , Ye An  1 , Shaogang Wang  1 , Qidong Xia  1
Affiliations
Review

The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

Xingyu Zhong et al. Cancers (Basel). .

Abstract

Background: Sex is an important factor influencing the immune system, and the distribution of tumors, including their types and subtypes, is characterized by sexual dichotomy. The aim of this study was to investigate whether there is an association between sex and the treatment effect of immune checkpoint inhibitors (ICI).

Methods: Four bibliographic databases were searched. Studies of randomized controlled trials (RCTs) assessing the efficacy of ICI were identified and used, and the primary endpoint was the difference in efficacy of ICI between males and females, presented as overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS). The study calculated the pooled HRs and 95% CIs for OS, PFS and RFS for males and females using a random effects model or a fixed effects model, and thereby assessed the effect of sex on the efficacy of ICI treatment. This study is registered with PROSPERO (CRD42022370939).

Results: A total of 103 articles, including a total of 63,755 patients with cancer, were retrieved from the bibliographic database, of which approximately 70% were males. In studies with OS as the outcome, the combined hazard ratio (HR) was 0.77 (95% CI 0.74-0.79) for male patients treated with ICI and 0.81 (95% CI 0.78-0.85) for female patients compared to controls, respectively. The difference in efficacy between males and females was significant.

Conclusions: ICI therapy, under suitable conditions for its use, has a positive impact on survival in various types of tumors, and male patients benefit more than females. It may be necessary to develop different tumor immunotherapy strategies for patients of different sexes.

Keywords: immune checkpoint inhibitors; immunotherapy; meta-analysis; randomized controlled study; sex.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Study selection PRISMA (preferred reporting items for systematic reviews and meta-analyses) flowchart for study selection for the systematic review on the effects of ICI, with data analyzed according to male and female subgroups. ICI, immune checkpoint inhibitors.
Figure 2
Figure 2
Characteristics of the studies. (A) Regional distribution of included studies and comparison of HR size between males and females (better for males represents a smaller HR for males and vice versa). (B) Male-to-female ratio of study subjects, with the number of males to females being approximately 1:1.6. (C,D) Proportion of study subjects by tumor type (C) and ICI drug type (D) to overall counts.
Figure 3
Figure 3
Hazard ratios for death in the intervention and control groups according to sex, with OS as the outcome. (The references cited in the figure are consistent with Table 1).
Figure 4
Figure 4
Subgroup analysis of hazard ratios for death in tumor patients stratified by tumor type and ICI drug type, by sex, with OS as the outcome.
See this image and copyright information in PMC

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