# Evaluation of sex differences in survival among glioblastoma patients treated with immune checkpoint inhibitors

## TL;DR

This study found no significant sex differences in survival outcomes for glioblastoma patients treated with immune checkpoint inhibitors.

## Contribution

The study provides clinical evidence on sex differences in ICI treatment outcomes for glioblastoma.

## Key findings

- In newly diagnosed GBM, ICI showed no sex difference in progression-free or overall survival.
- In recurrent GBM, males receiving ICI had worse overall survival but no significant sex-by-treatment interaction.
- No sex differences were observed when all immunotherapies were analyzed collectively.

## Abstract

Sex differences in glioblastoma (GBM) are recognized, but their treatment implications remain unclear. Recent preclinical studies have characterized mechanisms of sex-biased anti-tumor immunity in GBM, and have found in murine models that males derive greater survival benefit from immune checkpoint inhibitor (ICI). We evaluated sex differences associated with ICI in GBM patients.

We retrospectively evaluated consecutive patients with newly diagnosed GBM (nGBM) or recurrent GBM (rGBM) treated with ICI on clinical trials at one institution from 2014 to 2022. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis, univariate and multivariable regression models. Sex-by-treatment interactions were assessed relative to a concurrent reference group treated on non-ICI clinical trials.

296 patients with nGBM (58% male, 19% ICI) and 458 patients with rGBM (60% male, 40% ICI) were evaluated. In nGBM, ICI was not associated with sex difference in PFS (HRmale 1.35; 95% CI, 0.62–2.95; P = .446; Pinteraction = .142) or OS (HRmale 1.15 [0.53–2.53], P = .722; Pinteraction = .438) compared to non-ICI treatment. In rGBM, males receiving ICI had worse OS (HRmale 1.64 [1.09–2.47], P = .017) and trended towards worse PFS (HRmale 1.41 [0.94–2.11], P = .095), but sex differences with ICI were not significantly different compared to non-ICI treatment (PFS Pinteraction = .610; OS Pinteraction = .361). No sex differences were observed when all immunotherapies were analyzed collectively.

In nGBM and rGBM, ICI therapy was not associated with sex difference in PFS or OS. Clinically meaningful sex-based outcome differences may be better understood by prospective evaluation in clinical trials.