While this is not the first time research has highlighted more severe side effects among women undergoing chemotherapy, it’s the first comprehensive review of sex-based differences among patients undergoing immunotherapy and other targeted therapies for cancer.
The study did not discuss the specific types of adverse events that were detailed in the included clinical trials. A table showed that women were more likely to experience gastrointestinal issues, oral issues, sleep issues, and blood- and bone marrow-related issues than men.
These results of the new study, published last month in the Journal of Clinical Oncology, need to be confirmed, lead author Joseph M. Unger, PhD, an associate professor at the Fred Hutchinson Cancer Research Center in Seattle, told Verywell.
If confirmed, these results have major implications for cancer treatment. In our era of increasingly personalized medicine, sex may another criterion that should be taken into consideration when patients and providers choose a cancer treatment.
Discrepancy Is Greatest for Immunotherapy Side Effects
Cumulatively, women had a 34% greater risk of having a severe adverse event to cancer treatment compared to men. And among women who received immunotherapy, the risk was 49% greater.
“We knew from prior studies that women had worse side effects of chemotherapy treatments than men,” Unger said. “What was unstudied was whether that pattern was still prevalent in the newer therapies—the novel therapeutics, like immunotherapies and targeted therapies.”
But he doesn’t know why these differences are occurring.
“What was particularly surprising was the fairly dramatic difference and magnitude of the increased side effects for women compared to men in immunotherapy toxicities—a nearly 50% increased risk of severe toxicity for women compared to men for immunotherapies,” he added.
The study included data from over 23,000 patients who had been enrolled in 202 clinical studies conducted by a research organization known as the SWOG Cancer Research Network between 1980 and 2019. Researchers excluded studies regarding cancers specific to one sex, such as ovarian or testicular cancer.
About 38% of the enrolled patients were women and 62% were men. Unger says this is partially due to excluding clinical trials for breast cancer, but also reflects the typical ratio of women to men in the general cancer population.
Does This Change How Women Should Discuss Cancer Treatment With Their Oncologists?
What these findings mean for oncologists who are counseling individual patients about adverse effects of treatment remains to be seen.
“Some frontline colleagues tell me that this is a very meaningful finding, and it will potentially change how they provide guidance to women when it comes to what they can anticipate experiencing for certain kinds of treatments,” Unger said.
Others aren’t so sure yet.
“These observations—while they’re important, provocative, and will no doubt lead to additional research—don’t provide guidance at the clinical level,” Robert Dreicer, MD, associate director for clinical research and deputy director of the University of Virginia Comprehensive Cancer Center, told Verywell. Dreicer was not involved with the study. “We know that people may have certain differences in side effect profiles, but this [research] doesn’t tell you, if a patient walked in today, whether you’re going to treat her differently.”
The difference in how women and men react to cancer treatments has not been studied well, Dreicer adds.
“We know that there are some racial differences, but we haven’t thought about sex in that way,” he said.
Other Factors Influence Side Effect Risk
A patient’s sex is just one of several factors that can cause an increased risk side effects. Other factors may be more important to determining a course of treatment than that patient’s sex. For example, Dreicer says if a patient has poor kidney function, they’ll have trouble clearing a drug from their body, and be more likely to experience a negative reaction.
With immunotherapy, researchers don’t yet completely understand who will develop immune-related toxicity during treatment, and who won’t.
“We still don’t have a pretty good handle on that, let alone which factors might alter toxicity between men and women,” Dreicer said. “Like all things, [the new research] tends to produce more questions than answers.”
