Gender Does Not Influence Immunotherapy Response

An individual’s response to cancer treatment using an immune checkpoint inhibitor is not affected by their gender, according to study findings published in JAMA Oncology.

Immune checkpoint inhibitors are types of drugs that block certain proteins made by some types of immune system cells. Such proteins can include PD-1, PD-L1 and CTLA-4. “A (helpful analogy) is that checkpoint proteins are brakes on the immune system and checkpoint inhibitors release those brakes to allow the immune system to kill cancer cells,” Christopher J. D. Wallis, a resident in the division of urology at the University of Toronto, said in an interview with CURE®.

Previous research suggests that men have an advantage over women from immunotherapy treatment for advanced solid-organ cancers. “There is significant biologic rationale for differences in the immune system of men and women,” Wallis said. “Additionally, preliminary analysis of much more limited data suggested that women may not benefit from immunotherapy as much as men.”

Therefore, researchers decided to investigate this further using data from 23 different clinical trials, which included 13,721 patients — 9,322 (67.9%) men and 4,399 (32.1%) women. Most patients were in their 70s.

The studies included compared immunotherapy for metastatic cancers with other treatment regimens, such as chemotherapy and targeted therapies. The majority of the trials analyzed were for patients with non-small cell lung cancer (48%), followed by melanoma (17%), and clear cell renal cell carcinoma and small cell lung cancer (9% each). Trials of urothelial carcinoma, head and neck squamous carcinoma, mesothelioma and gastric or gastroesophageal carcinoma made up 4% each of those included.

In addition, most of the trials used examined patients given immunotherapy after a previously failed therapy. Eleven evaluated overall survival in the first-line setting. A PD-1 or PD-L1 inhibitor was the therapy used in most of the trials. However, 26% used a CTLA-4 inhibitor, such as Yervoy (ipilimumab).

After analysis, the researchers determined no significant difference in treatment efficacy or overall survival between men and women. “Immunotherapy is equally efficacious, compared to standard systemic therapy, in men and women with advanced cancer,” Wallis said.

Overall, Wallis said that a patient's gender should not influence the decision whether they are appropriate candidates for immunotherapy.

However, Wallis explained that more research is needed, “given what is known about differential autoimmune disease prevalence in women and men to understanding how the immune system of men and women may respond to cancer and cancer therapies differently.”