Women more likely to experience severe toxicity from cancer treatment
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Women receiving cancer treatment in clinical trials exhibited higher risk for severe symptomatic and hematologic adverse events than their male counterparts, according to a study.
These findings remained consistent across multiple treatment modalities, including immunotherapy, chemotherapy and targeted therapy, researchers noted.
“Although there has been evidence that women are at greater risk [for] severe toxicity than men in classic cytotoxic trials, it hadn’t been looked at in a large database for contemporary treatment paradigms such as immunotherapies and targeted therapies,” Joseph M. Unger, PhD, MS, associate professor in the cancer prevention program in the public health services division at Fred Hutchinson Cancer Research Center, told Healio. “We also realized that no previous studies have examined whether patient-reported outcomes, which measure the patients’ treatment experience and have been shown to predict cancer outcomes, may be used to identify differences in the risk [for adverse events].”
Unger spoke with Healio about the study findings, which he presented at this year’s American Association for Cancer Research Annual Meeting, and their potential implications for clinical practice.
Healio: How did you conduct this study?
Unger: We have a large database of trials that has been generated over many decades. So, I set some criteria, going back 40 years, and included trials that met those criteria. In particular, we looked at cancers that were not sex-specific, so we didn’t include breast or prostate cancers. We ended up compiling 202 trials with nearly 24,000 patients and nearly 300,000 severe adverse event experiences among those patients. Then we looked at them according to categories, including different treatment types and adverse event types, and analyzed those by sex. We found compelling evidence that it is not just in the cytotoxic therapy setting where we experience a greater risk for severe adverse events. It’s also modern treatments, especially immunotherapies. We found that in this setting, women had almost a 50% increased risk for severe toxicity.
Healio: What do you think is driving these differences?
Unger: The study itself doesn’t answer this, but it does offer some opportunities to hypothesize. I believe we can rule out some things. For instance, there has been a concern that this is due to relative dose differences between men and women at different body sizes. We adjusted for obesity status, so we were able to account for that. There has also been a concern that medication adherence might differ between men and women, but we’re in a trial setting in this analysis, so that’s probably not much of a concern. I think the big issue is the concern that there may be biases in how men and women report symptomatic adverse events, which are the more subjective type of adverse events. However, there were also big differences in hematologic adverse events. Women have a much greater risk for hematologic adverse events, which are a very objective measure. So, we ruled that out, too, and it led us to wonder, what are the potential biologic differences? Perhaps the way the body processes drugs is different. Inflammatory response patterns could differ between men and women; there could even be differences in the way the microbiome behaves. It certainly advances the hypothesis that these are potential avenues of research. It would be really critical to understand why.
Healio: Is there anything else you’d like to mention about this?
Unger: One thing of particular interest in my presentation at AACR was that the way we defined symptomatic adverse events in our trial was not patient-reported, but rather physician-reported. We wanted to take the next step and see how patient-reported outcomes may predict toxicity and adverse events, including by sex. The analysis showed that when you look at a common patient-reported outcome — fatigue — patients with increased levels of baseline fatigue had a much higher risk for severe toxicity, and that applies to both men and women. It was even a slight bit of gradient in terms of increased risk for men. Still, it was meaningful for both sexes and substantial.
For more information:
Joseph M. Unger, PhD, MS, can be reached at Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109; email: junger@fredhutch.org.
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Unger JM, et al. Abstract SY43-03. Presented at American Association for Cancer Research Annual Meeting; April 14-19, 2023; Orlando.
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