Men With Advanced Cancers Respond Better Than Women to Immune Checkpoint Inhibitors

A recent systematic review and meta-analysis published in The Lancet Oncology found that men with advanced cancers respond better than women to treatment with anti-PD-1 or anti-CTLA-4 immune checkpoint inhibitors.

Researchers identified 20 eligible randomized controlled trials of immune checkpoint inhibitors (ipilimumab, tremelimumab, nivolumab, or pembrolizumab) that reported overall survival according to patients’ sex. The 20 randomized trials were comprised of a total of 11,351 patients with advanced or metastatic cancers (7646 [67%] men and 3705 [32%] women).

The pooled overall survival hazard ratio (HR) was 0.72 (95% CI 0.65-0.79), or 28% lower risk of death in male patients treated with immune checkpoint inhibitors, compared with men treated standard therapies in control groups. In women treated with immune checkpoint inhibitors, the pooled overall survival was 0.86 (95% CI 0.79-0.93), or 14% lower risk of death compared with control groups. Researchers identified that the difference in efficacy between men and women treated with immune checkpoint inhibitors was significant, P = .0019.

“Immune checkpoint inhibitors can improve overall survival for patients with advanced cancers such as melanoma and non-small cell lung cancer, but the magnitude of benefit is sex-dependent. The pooled reduction of risk of death was double the size for male patients than for female patients,” noted the study authors.

Based on these findings, the authors have recommended that a patient’s sex “should be taken into account in the assessment of risk versus benefit when making decisions about treatment strategies.”

Future research should look to optimize immunotherapies for female patients, and clinical trials should strive to include more women to better ensure they capture a potential therapies’ effectiveness more effectively.

As “immune checkpoint inhibitors are associated with specific adverse events, efforts are ongoing to identify predictive biomarkers” that may be able to identify patients that are most likely to “derive the maximum benefit” from a specific treatment. These efforts must be aware of “sex-related differences in the benefit[s] achievable from immunotherapies.” However, to date it “remains an under-investigated issue.”

Reference

Conforti F, Pala L, Bagnardi V, et al. Cancer immunotherapy efficacy and patients’ sex: a systematic review and meta-analysis [published online May 16, 2018]. Lancet Oncol. doi.org/10.1016/S1470-2045(18)30261-4