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Advanced melanoma nivolumab–ipilimumab outcomes may be poorer in women

By Lynda Williams, medwireNews Reporter

Women may derive less benefit from combination immune checkpoint inhibitor (ICI) therapy for advanced melanoma than men, suggest study findings published in JAMA Network Open.

Grace Lu-Yao, from the Sidney Kimmel Cancer Center in Philadelphia, Pennsylvania, USA, and co-workers found that the outcome of nivolumab plus ipilimumab treatment was influenced by patient sex.

Specifically, women who had previously received ipilimumab were a significant 2.06 times more likely to die than their male counterparts after adjusting for age at last ICI therapy initiation, cancer stage, comorbidity score and autoimmune disease.

On the other hand, there was no significant difference in the survival of women versus men who were given PD-1 inhibitor monotherapy with pembrolizumab or nivolumab, regardless of whether the patients had prior use of ipilimumab (39.8 vs 41.0%) or not (40.6 vs 45.1%).

But further analysis among women who had previously used ipilimumab revealed that receipt of combination therapy was associated with a significant 2.82 times higher rate of mortality than use of PD-1 inhibitor monotherapy.

By contrast, no such difference in survival was found among men given combination versus PD-1 monotherapy regimens, regardless of history of ipilimumab use, the researchers say.

“These novel findings suggest that, for women with a prior history of ipilimumab, treatment with anti–PD-1 therapy may be preferable to combination therapy, whereas for men, it is unclear which treatment is better”, write Lu-Yao et al.

The team identified the sex-related effectiveness differences after collating data from 1369 patients aged at least 65 years who were diagnosed with stage III–IV melanoma between 1991 and 2015. The patients were recorded in the Surveillance, Epidemiology, and End Results–Medicare linked database as having had a last ICI regimen of nivolumab plus ipilimumab, or monotherapy with nivolumab or pembrolizumab, and were followed-up until 2017.

The majority (71.7%) of the patients were men and the median age was 75 years; 12.1% of the group were diagnosed with one or more autoimmune disorders and this was more common in women than men (17.3 vs 10.0%).

“By design, this population-based cohort study ensured that the patient cohort was representative of patients with advanced melanoma in real life”, the researchers comment.

The team hypothesizes that sex-based tumour differences in tumour mutation burden or neoantigens may explain the differences in ICI response between men and women, noting that ipilimumab and PD-1 inhibitors work at different points in the T-cell regulatory pathway and therefore “may interact differently with sex-specific biomarkers.”

The researchers remark that “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”, they recommend.

News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Netw Open 2021; 4: e2136823