Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials
Open Access
- 12 December 2018
- journal article
- research article
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 7 (12), 542
- https://doi.org/10.3390/jcm7120542
Abstract
Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p < 0.001 and HR 0.77, p < 0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p < 0.012), with the exception of melanoma (in women, HR 0.80, p = 0.006). PFS was longer in men than in women (HR 0.67, p < 0.001 and HR 0.77, p = 0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.Keywords
Other Versions
This publication has 64 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced MelanomaJournal of Clinical Oncology, 2013
- Gender Differences in Cancer Susceptibility: An Inadequately Addressed IssueFrontiers in Genetics, 2012
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaThe New England Journal of Medicine, 2010
- Heart Disease and Stroke Statistics-2010 Update A Report From the American Heart AssociationCirculation, 2010
- Two Different Mechanisms of Myocardial Ischemia Involving 2 Separate Myocardial Segments in a Patient With Normal Coronary AngiographyCirculation, 2010
- The X-files in immunity: sex-based differences predispose immune responsesNature Reviews Immunology, 2008
- Therapeutic implications of the gender-specific aspects of cardiovascular diseaseNature Reviews Drug Discovery, 2006
- Measuring inconsistency in meta-analysesBMJ, 2003
- Advanced methods in meta‐analysis: multivariate approach and meta‐regressionStatistics in Medicine, 2002