Is Patient Sex Associated With Immunotherapy Efficacy?

There was no statistically significant association between whether a patient is a man or a woman and the efficacy of immunotherapy on overall survival for the treatment of advanced solid tumors, according to the results of an updated analysis.

These results are in contrast to those published in a previous meta-analysis that suggested that men derived greater benefit from immunotherapy compared with women.

“We found no evidence that sex should be considered when deciding whether to offer immunotherapy to patients with advanced cancer,” Christopher J.D. Wallis, MD, PhD, of the University of Toronto, Canada, and colleagues wrote in JAMA Oncology.

According to the authors, the previous meta-analysis by Conforti et al included a limited subset of immunotherapeutic agents, and did not include several studies with “more robust representation of female patients” that have been published since their literature review.

“Trials with an underrepresentation of women may present spurious results for sex-specific subgroup analyses, as evidenced by the wide confidence intervals when less than 20% of the cohort represented is women,” Wallis and colleagues wrote. “Six of the 7 trials included in this meta-analysis but not included in the Conforti et al study had more than 27% women representation, with 2 trials having more than 38% women inclusion.”

The researchers also noted that they excluded three trials included in the Conforti analysis that compared various immunotherapy regimes.

This updated analysis included 23 randomized clinical trials that included 9,322 men and 4,399 women. Patients had a variety of solid tumors including non-small cell lung cancer, melanoma, renal cell carcinoma, urothelial carcinoma, head and neck squamous carcinoma, mesothelioma, and gastric cancer. Included trials tested both PD-L1 and PD-1 inhibitors, and CTLA-4 inhibitors.

The median age of included patients was in the 70s. Patients in these trials that received immunotherapy had a significant overall survival advantage compared with other systemic therapies (Hazard Ratio [HR], 0.75; 95% CI, 0.70–0.81; P < .001). Both men (HR = 0.75; P < .001) and women (HR = 0.77; P = .002) treated with immunotherapy had an overall survival advantage with immunotherapy compared with standard of care systemic treatment.

No statistically significant difference for overall survival advantage was found between men and women treated with immunotherapy. Subgroup analyses looking at disease site, line of therapy, class of immunotherapy, and study methodology confirmed this finding.

The researchers noted that they excluded several trial that lacked published sex-subgroup analyses and that these studies “may demonstrate sex differences if analyzed in this fashion.”