Key PointsQuestion
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.
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.