Research Paper Volume 13, Issue 11 pp 15413—15432

Sex-related differences in the efficacy of immune checkpoint inhibitors in malignancy: a systematic review and meta-analysis

Li-Ting Lai1, , Wei-Guo Gu1, , Ming-Bin Hu1, , Wei-Jia Wang2, , Shan-Shan Wang2, , Ya-Jun Huai1, , Jin-Hong Mei2, *, , Chun-Liang Wang3, *, ,

  • 1 Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
  • 2 Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
  • 3 Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
* Equal contribution

Received: January 11, 2021       Accepted: May 14, 2021       Published: June 4, 2021
How to Cite

Copyright: © 2021 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Although disease susceptibility is known to differ between men and women, it is controversial whether the efficacy of immune checkpoint inhibitors for malignancies also differs between the sexes. We conducted a meta-analysis to explore the impact of sex on immune checkpoint inhibitor treatment outcomes. We searched PubMed, Embase and the Cochrane Library databases from inception to October 1, 2020 for randomized controlled trials of immune checkpoint inhibitors with hazard ratios (HRs) stratified by sex. We calculated the pooled HRs for men and women using the ln(HR), and assessed the heterogeneity between the two estimates through an interaction test. In total, 22,268 patients from 39 randomized controlled trials were included. Immune checkpoint inhibitors yielded better overall survival than conventional agents in both men (HR: 0.75, 95% confidence interval [CI]: 0.71–0.80) and women (HR: 0.77, 95% CI: 0.70–0.85). Progression-free survival benefits were also observed in both men (HR: 0.64, 95% CI: 0.58–0.70) and women (HR: 0.67, 95% CI: 0.58–0.77) treated with immune checkpoint inhibitors. No sex differences in the response to immune checkpoint inhibitors were found when overall survival and progression-free survival were used as the endpoints.


CTLA-4: cytotoxic T-lymphocyte-associated protein 4; PD-1: programmed cell death 1; PD-L1: programmed cell death 1 ligand 1; CI: confidence interval; HR: hazard ratio; NSCLC: non-small cell lung cancer; OS: overall survival; PFS: progression-free survival.