Women With Advanced Melanoma May Experience Less Benefit From ICIs vs Men

Women treated with immune checkpoint inhibitors such as nivolumab (Opdivo) plus ipilimumab (Yervoy) or anti–PD-L1 therapies such as nivolumab or pembrolizumab (Keytruda) for advanced melanoma may not experience the same benefit as male patients, according to a study published in JAMA Network Open.

For women receiving ipilimumab, the mortality ratio was 2.06 times higher (95% CI, 1.28-3.32; P = .003) than men. Investigators did not observe a difference between women or men receiving anti–PD-L1 therapy with (HR, 0.97; 95% CI, 0.68-1.38; P = .85) or without previous ipilimumab (HR, 0.85; 95% CI, 0.67-1.07; P = .16). Among who women were previously treated with ipilimumab, the mortality risk was 2.82 times higher (95% CI, 1.73-4.60) with the combination therapy vs anti-PD-L1 therapy.

“In this population-based cohort study, we observed that female patients with advanced melanoma treated with nivolumab plus ipilimumab combination therapy had an overall mortality risk 2 times higher than their male counterparts after adjusting for known confounding variables. Further research is warranted to validate our findings, to explore potential biological mechanisms, and to design optimal treatment strategies tailored to each patient,” investigators of the study wrote.

A total of 1369 patients were enrolled on the study, including 982 men and 387 women. Patients had a median age of 75 years. Overall, 1204 patients received anti–PD-L1 therapy, and 165 received the combination therapy. Patient characteristics were similar except for a significant proportion of women having an autoimmune disease vs men.

Distribution of death was similar between the 2 groups that received treatment with anti–PD-1 therapy regardless of treatment with ipilimumab. The distribution of death was not equal for those receiving combination therapy, including 26 women and 50 men.

Investigators followed patients for 24 months, and median survival was not reached for either sex. Additionally, the was not a significant difference in survival between the groups. The median survival was only reached for women receiving nivolumab/ipilimumab at 10.2 months (95% CI, 4.6-23.9). Over 50% of patients who received anti–PD-L1 therapy had survived by the end of the study, 473 of whom had not received prior ipilimumab, and 215 had received prior ipilimumab. Investigators did not find a difference in survival between male and female patients receiving anti-PD-L1 therapy.

“Despite the accumulating evidence of the potential role played by sex in drug effectiveness owing to the biological differences between men and women, the effectiveness of new therapeutic approaches is rarely examined by sex.31,32 This lack of attention on the association of sex with the effectiveness of ICI-based immunotherapy may have significant negative consequences, especially because these treatments are associated with high toxicity and high treatment cost. For future trials, it would be crucial to examine effect modification by sex,” the investigators concluded.

Reference

Jang SR, Nikita N, Banks J, et al. Association between sex and immune checkpoint inhibitor outcomes for patients with melanoma. JAMA Netw Open. 2021;4(12):e2136823. Published 2021 Dec 1. doi:10.1001/jamanetworkopen.2021.36823