PreprintArticleVersion 3Preserved in Portico This version is not peer-reviewed
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
Version 1
: Received: 16 August 2018 / Approved: 17 August 2018 / Online: 17 August 2018 (12:46:57 CEST)
Version 2
: Received: 15 September 2018 / Approved: 17 September 2018 / Online: 17 September 2018 (08:44:11 CEST)
Version 3
: Received: 15 November 2018 / Approved: 15 November 2018 / Online: 15 November 2018 (07:02:24 CET)
Grassadonia, A.; Sperduti, I.; Vici, P.; Iezzi, L.; Brocco, D.; Gamucci, T.; Pizzuti, L.; Maugeri-Saccà, M.; Marchetti, P.; Cognetti, G.; De Tursi, M.; Natoli, C.; Barba, M.; Tinari, N. 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. J. Clin. Med.2018, 7, 542.
Grassadonia, A.; Sperduti, I.; Vici, P.; Iezzi, L.; Brocco, D.; Gamucci, T.; Pizzuti, L.; Maugeri-Saccà, M.; Marchetti, P.; Cognetti, G.; De Tursi, M.; Natoli, C.; Barba, M.; Tinari, N. 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. J. Clin. Med. 2018, 7, 542.
Grassadonia, A.; Sperduti, I.; Vici, P.; Iezzi, L.; Brocco, D.; Gamucci, T.; Pizzuti, L.; Maugeri-Saccà, M.; Marchetti, P.; Cognetti, G.; De Tursi, M.; Natoli, C.; Barba, M.; Tinari, N. 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. J. Clin. Med.2018, 7, 542.
Grassadonia, A.; Sperduti, I.; Vici, P.; Iezzi, L.; Brocco, D.; Gamucci, T.; Pizzuti, L.; Maugeri-Saccà, M.; Marchetti, P.; Cognetti, G.; De Tursi, M.; Natoli, C.; Barba, M.; Tinari, N. 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. J. Clin. Med. 2018, 7, 542.
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.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
