Impact of Biological Sex in Cancer Immunotherapy Outcomes

Immunotherapy for cancer, also called immuno-oncology, is a form of treatment that uses the body’s immune system to not only prevent malignant diseases, but also to control and eliminate cancer.

Cancer immunotherapy has the power to:

  • Help the immune system recognize and attack cancer cells
  • Enhance immune cells to assist them in eliminating cancer
  • Give the body additional components to boost the immune response

Cancer immunotherapy has many forms, including checkpoint inhibitors, targeted antibodies, adoptive cell transfer, cytokines, adjuvants, cancer vaccines, and tumor-infecting viruses. 

Immunotherapy uses materials from living organisms to combat diseases. Some immunotherapies utilize genetic engineering to boost the cancer-fighting capabilities of immune cells. Doctors call these treatments gene therapies. Many immunotherapies are also for the prevention, treatment, and management of different cancer types. Oncologists can order these treatments in combination with more conventional methods, including chemotherapy, radiation, and surgery to improve their effectiveness.

However, a growing concern among patients and oncologists alike is that cancer immunotherapy may be more effective in men than in women. In this article, we will discuss the impact of biological sex on immunotherapy outcomes. 

The Research: Does Sex Affect Immunotherapy Outcomes?

Cancer immunotherapy using checkpoint inhibitors, to be specific, may reduce mortality rates in men compared to women, according to a recent study.

In the 2018 meta-analysis and systematic research published in Lancet Oncology, the researchers examined 20 randomized controlled trials of immune checkpoint inhibitors that included detailed information on overall survival and the patients’ biological sex. Altogether, the studies involved 11,351 people with advanced or metastatic cancers.

Cancer Types and Immunotherapy Drugs Reviewed in the Meta-Analysis

The study’s overall target group included two-thirds male patients and one-third female patients. The checkpoint inhibitors used were tremelimumab, nivolumab, ipilimumab, and pembrolizumab. The patients involved had non-small cell lung cancer, head and neck cancer, melanoma, bladder tumors, renal cell carcinoma, mesothelioma, or gastrointestinal tumors.

The Results: Male-Biased Outcome

The authors found that although male patients who received treatment with checkpoint inhibitors had a 28 percent reduced risk of mortality, compared to the opposite sex, the survival advantage among female patients was smaller at 14 percent reduced risk of death.

Dr. Fabio Conforti, MD, from the European Institute of Oncology in Milan and the co-author of the study commented that the magnitude of the difference observed between the outcome seen in male patients versus female patients was clinically significant.

The authors wrote, “The pooled reduction of risk of death was double the size for male patients than for female patients — a difference that is similar to the size of the difference in survival benefit observed between patients with non-small cell lung cancer with PD-L1 positive (greater than 1 percent) tumors versus negative tumors, who were treated with anti-PD-1.”

The difference in outcomes observed in men and in women was clear across all the subgroups in the meta-analysis, which included subgroups classified based on cancer variety, line of treatment, medicine used, and type of control.

In addition, there was significantly greater heterogeneity in the effectiveness of checkpoint inhibitors on mortality incidence in men than in women. The authors advised that the phenomenon might be explained by the fact that the medication used has lower efficacy in women. Thus, it may lower the variability of outcomes when compared with those in male patients.

The researchers also analyzed whether the studies comparing immunotherapies with non-immunological treatments showed a different effect, but they still found a higher benefit in male patients.

Addressing the Role of Male-Biased Mortality

In general, men have almost double the risk of death from cancer than women, said the authors, with the biggest differences seen in those with melanoma, lung cancer, esophageal cancer, laryngeal cancer, and bladder cancer.

“This male-biased mortality is hypothesized to reflect differences not only in behavioral and biological factors, including causes of cancer and hormonal regulation, but also in the immune system.”

Despite it all, biological sex or gender is almost never taken into account when scientists test new therapeutic approaches, the authors noted.

Not Enough Women in Medical Trials

They also made remarks about the noticeably low number of female participants included in each clinical trial — a concern that has been recognized and criticized as far back as the early 1990s.

“Our results further highlight this problem, showing clinically relevant differences in the efficacy of two important classes of immunological drugs, namely anti–CTLA-4 and anti–PD-1 antibodies, when compared with controls in male and female patients with advanced solid tumors,” the authors wrote.

They also commented that they could not bypass the possibility that the results may be because of other variables distributed differently between the male and female patients. However, they said that variables known to impact the efficacy of immune checkpoint inhibitors, like PD-L1 expression and mutation status, were unlikely to explain the results.

Conclusion: Should Oncologists Consider the Patient’s Sex?

As a result of their findings, the researchers said that doctors should take a cancer patient’s biological sex into account when weighing the risks and benefits of immune checkpoint inhibitors, particularly since the magnitude of benefit was dependent on gender. They also revealed that future studies on immunotherapy should include more women.

Why You Should Still Consider Immunotherapy

The Food and Drug Administration (FDA) has approved certain immunotherapies in the United States, and many other countries already treat a variety of cancers using this approach. The FDA approvals are a result of decades of research and clinical testing designed to determine the effectiveness of more alternative cancer treatments.

Although scientists and doctors have not yet mastered or learned all the immune system’s cancer-fighting abilities, immunotherapy treatments are already helping to extend and save the lives of several patients. Plus, it still has the potential to become more personalized, more precise, and more effective than current cancer treatments available.

Get the Treatment You Need From Experts in Immunotherapy

Here at New Hope Unlimited, among the innovations we offer to cancer patients is immunotherapy. If you are looking for a treatment that uses certain parts of the immune system to fight cancer instead of harmful drugs and invasive techniques, then immunotherapy is the answer.

Find out if you are a candidate for cancer immunotherapy. Call us at 480-757-6573 today to schedule your consultation.

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