IMMUNOTHERAPY has changed the lives of people with advanced melanoma. If once the disease in the metastatic phase did not leave much hope, today after 5 years from the diagnosis more than 50-60% of patients are alive. However, this treatment, which essentially works by setting the immune system on and off against tumor cells, doesn’t work the same for everyone. Some patients respond very well to treatment, but for others, for the same treatment, mortality is higher. Especially for others one would say, according to a population study published in Jama Network Open: data show that women have twice the mortality rate of men.
Real-world data
What we are talking about “is the first study in a large patient population that indicates a significant difference in survival for women treated with a combination of two checkpoint inhibitors,” explains Grace Lu-Yao, senior author of the study. But are women more likely to die because the therapy works less, or because of the side effects? We don’t know yet – admits Lu-Yao – however we have a strong signal from the real world that tells us that we should investigate more ”. We should if only because we already know that women’s and men’s immune systems are slightly different. Women, for example, as the authors of the work on Jama recall, have a higher risk of autoimmune diseases, but tend to have stronger immune responses against infections.
Melanoma: Survival increases, but more for men
by Tina Simoniello
More marked gender difference for combination therapy
Going back to the study, Lu-Yao’s team analyzed the medical records of nearly 1,400 patients with advanced melanoma diagnosed between 1991 and 2015, and treated with one or more checkpoint inhibitors, such as pembrolizumab, nivolumab, or ipilimumab. The records were collected in SEER-Medicare, a US national database. In practice, the authors relied on information obtained not from controlled and randomized trials, but on medical records. The result? When treated with a single immune checkpoint inhibitor, men and women showed no difference in survival. When the checkpoint inhibitors were two, administered in combination (nivolumab and ipilimumab), things changed: in this case the survival of men was much greater: the mortality rate was 40% for both sexes with single anti-PD-1 therapy, while with combined therapy it remained at 40% in men and rose to 65% in women. It is clear that this is a difference that must be investigated, also because we are talking about treatments that are in any case associated with toxicity and high costs. “Our data are a wake-up call based on the experience of hundreds of patients. They are real-world data that show that the results obtained in men may not be applicable to women and – concluded Lu-Yao – it is essential to design studies. who are able to evaluate the efficacy of the treatment on the basis of sex “.
Immunotherapy: Women have twice as many side effects as men
by Tina Simoniello
But real world data is not enough
“The study is interesting because it confirms evidence that has already emerged on the differences in response to immunotherapy between the two genders”, comments Paolo Ascierto, medical director at the complex operating unit of Medical Oncology and Innovative Therapies of the National Cancer Institute-Pascale Foundation of Naples. “It is based on data from a large number of patients, however we cannot take these results as absolute truths, but we should verify them prospectively. We do not know why these women died: whether from disease progression or from the toxicity associated with the treatments, whether they were treated in high-volume or peripheral centers, which perhaps did not have sufficient experience in the treatment of toxicities. The issue of gender difference – concludes Ascierto – is certainly very interesting and has been under study for some time, but we must pay close attention to the data obtained from retrospective analyzes. There is a series of elements and variables that must be considered, and which escape real world studies. We need prospective data, which give us cleaner information ”.
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