medwireNews: Women undergoing cancer treatment have a significantly higher risk for severe treatment-related adverse events (TRAEs) than men, particularly if they are receiving immunotherapy, shows an analysis of data from more than 200 clinical trials.
Joseph Unger (Fred Hutchinson Cancer Research Center, Washington, Seattle, USA) and colleagues say their findings “support the idea that sex may independently modulate drug toxicity, including for novel treatments.”
The researchers report in the Journal of Clinical Oncology that women are a significant 34% more likely to experience a severe TRAE (grade 3 or worse) than men during treatment with cytotoxic chemotherapy, immunotherapy, or targeted therapy overall, after adjustment for age, race, BMI, and disease prognosis.
During immunotherapy the risk for a severe TRAE is a significant 49% higher for women than men, while for chemotherapy and targeted therapy it is a significant 36% and 25% higher, respectively.
The data are derived from 202 phase 2 and 3 clinical trials conducted between 1980 and 2019, that excluded studies of sex-specific cancers. Together the trials included 23,296 patients (37.9% women) who experienced 274,688 TRAEs from 13 symptomatic and 14 objective AE categories. Of these, 64.6% experienced at least one severe TRAE.
In total, 17,417 participants received cytotoxic chemotherapy, 2319 received immunotherapy, and 3560 received targeted therapy. The most common cancers included in the studies were gastrointestinal (26.1%), lung (20.5%), and leukemia (12.1%).
Compared with men, women had significantly higher rates of symptomatic (33.3 vs 27.9%), objective hematologic (45.2 vs 39.1%), and objective, nonhematologic (30.9 vs 29.0%) TRAEs overall, corresponding to significant 33%, 30%, and 8% increased odds for these events after adjustment for confounders.
By treatment and AE type, the greatest risk difference was for symptomatic TRAEs among women receiving immunotherapy. In this case women were a significant 66% more likely to experience a severe TRAE than men, with rates of 33.7% versus 25.4%.
Unger and team also found that, across 295 evaluable comparisons that included all 27 symptomatic and objective AE categories, there were 68 instances (23.1%) where women had a significantly increased risk for specific AE category at a given grade cut point compared with five instances among men (1.7%).
For example, women receiving chemotherapy had significantly increased risks for severe symptomatic skin, oral, gastrointestinal, and sleep-related TRAEs than men.
Severe symptomatic gastrointestinal and sleep-related TRAEs were also more common among women receiving immunotherapy, as were objective cardiovascular and hematologic events.
Of note, the risk for objective, nonhematologic TRAEs was similar for women and men across the three treatment types.
Unger et al conclude that “more awareness of symptom differences or reporting differences in women versus men is needed.”
They add: “A better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women (in particular).”
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