Gender May Play a Role in Immunotherapy Efficacy, Further Studies Are Warranted

Jessica Skarzynski

Immunotherapy continues to evolve as a treatment option for various cancers; however, men may see more benefit from it more than women, according to a study published in The Lancet Oncology.

Both sex and gender could affect the strength of the body's immune response, according to the researchers; for example, women generally show stronger immune responses than men in reaction to medical treatment, lead author, Fabio Conforti, M.D., from the European Institute of Oncology in Milan, Italy, explained in a press release.

Because little is known about the effect of patients' sex on the efficacy of immune checkpoint inhibitors as cancer treatments, the researchers performed a systematic review and meta-analysis to determine the heterogeneity of immune checkpoint inhibitor efficacy between men and women.

The review and meta-analysis included 20 previously published randomized trials and examined data from 11,351 individuals (7,646 men and 3,705 women). This group included patients with advanced or metastatic melanoma (3,632 patients; 32 percent), non-small cell lung cancer (3,482 patients; 31 percent), renal cell carcinoma, urothelial cancer and head and neck cancer – all of which received an immune checkpoint inhibitor.

In analyzing the data, the researchers found immunotherapy to be more effective than other treatments or not treatment at all in both men and women. However, male patients’ survival rates were nearly double that of female patients.

Although the reason for this is unknown, Conforti noted, “women account for roughly 80 percent of all patients with systemic autoimmune diseases worldwide. Therefore, it's possible that differences in the immune system of women and men could be relevant to the natural course of chronic inflammatory conditions such as cancer, and potentially how they respond to drugs."

In addition to the fact that the analysis relied on published results and not individual patient data, the researchers acknowledged that the larger male population may have made it difficult to draw any definitive conclusions.
They added that this highlights the widely recognized problem of female under-representation in clinical trials. It also lends credibility to the idea that further sex-specific research should be done, considering individual trials for both genders are too statistically small to reliably prove any correlation between sex and efficacy.

Given these limitations, Conforti concluded that further research is needed to better understand the differences in effectiveness to ultimately improve treatments for all patients.

"Despite the available evidence on the potential role played by sex in influencing how drugs work, trials testing new therapies rarely take sex into account,” Conforti said. “As we seek to improve immunotherapy further by identifying predictive biomarkers of response, sex differences should be further investigated."

In an accompanying editorial, Omar Abdel-Rahman of Ain Shams University (Egypt) and the University of Calgary, Canada, took that conclusion a step further. “Although the article by Conforti and colleagues is a thought-provoking and hypothesis-generating piece of work, caution needs to be exercised before jumping directly to radical conclusions and before changing the current standard of care among approved indications for immune checkpoint inhibitors.”
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