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Original Investigation
January 3, 2019

Association of Patient Sex With Efficacy of Immune Checkpoint Inhibitors and Overall Survival in Advanced Cancers: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
  • 2School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
  • 3Center for Outcomes Research, Department of Urology, Houston Methodist Hospital, Houston, Texas
  • 4Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California
  • 5Urology Section, Durham VA Medical Center, Durham, North Carolina
  • 6Moores Cancer Center-La Jolla, Department of Medicine, University of California, San Diego, La Jolla
  • 7Translational Research & Immunooncology, The Angeles Clinic & Research Institute, Los Angeles, California
  • 8Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California
  • 9Division of Urology, Department of Surgery, Medical College of Georgia at Augusta University, Augusta
  • 10Georgia Cancer Center, Augusta University, Augusta, Georgia
JAMA Oncol. Published online January 3, 2019. doi:10.1001/jamaoncol.2018.5904
Key Points

Question  Do women derive less advantage from immune checkpoint inhibitors, compared with standard systemic therapy, in the treatment of advanced solid-organ malignant neoplasm?

Findings  In this systematic review and meta-analysis of 23 randomized clinical trials of immunotherapy for advances solid-organ cancers including 9322 men and 4399 women, overall survival from immunotherapy was found in both men and women, with no statistically significant differences between the sexes.

Meaning  The response to immune checkpoint inhibitors does not appear to differ on the basis of patient sex.

Abstract

Importance  Sex-associated differences in immune response are known, but a meta-analysis suggested men, compared with women, derive greater value from immunotherapy for advanced solid-organ malignant neoplasms. However, methodologic concerns and subsequent trials have placed these results in doubt.

Objective  To perform an updated, comprehensive meta-analysis that assesses the efficacy of immunotherapy in advanced cancers according to patient sex.

Design, Setting, and Participants  A systematic review of studies (n = 23) indexed in MEDLINE (PubMed), Embase, and Scopus from inception of these databases to October 2, 2018, was conducted. Randomized clinical trials that compared immunotherapy with standard of care in the treatment of advanced solid-organ malignant neoplasms were included if overall survival was reported as an outcome and if data stratified by patient sex were available. Observational studies, editorials, commentaries, review articles, non–peer-reviewed publications, studies that compared various immunotherapy regimens, studies that reported other measures of oncologic response, and studies that reported subgroup analyses for 1 sex only were excluded.

Main Outcomes and Measures  Overall survival, with a test for heterogeneity between women and men, to assess the null hypothesis that no difference in the survival advantage of immunotherapy exists by patient sex.

Results  This meta-analysis included 23 randomized clinical trials that reported on 9322 men (67.9%) and 4399 women (32.1%); the age of most patients was in the 70s. An overall survival benefit of immunotherapy was found for both men (hazard ratio [HR], 0.75; 95% CI, 0.69-0.81; P < .001) and women (HR, 0.77; 95% CI, 0.67-0.88; P = .002). Random-effects meta-analysis of study-level differences in response to immunotherapy demonstrated no statistically significant difference between the sexes (I2 = 38%; P = .60). Subgroup analyses according to disease site, line of therapy, class of immunotherapy, study methodology, and representation of women recapitulated these findings.

Conclusions and Relevance  Stratified analyses demonstrated no statistically significant association of patient sex with the efficacy of immunotherapy in the treatment of advanced cancers using overall survival as the outcome.

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