Women have a significantly higher risk of severe symptomatic adverse events (AEs) and hematologic AEs, compared with men, in response to multiple cancer treatments, according to research published in the Journal of Clinical Oncology.

The study revealed a 34% increased risk of severe AEs in women compared with men (odds ratio [OR], 1.34; 95% CI, 1.27-1.42; P <.001). Large sex differences in AEs were found particularly in patients receiving immunotherapy.

Treatment-related AEs were analyzed by sex using combined data from SWOG phase 2 and 3 cancer trials conducted between 1989 and 2019, excluding sex-specific cancers.

Continue Reading

The study cohort included 23,296 patients enrolled in 202 trials, 8838 who were women and 14,458 who were men. The patients experienced 274,688 AEs in total.

In the overall population, 34.7% of patients were 65 years or older, 9.0% were Black, and 25.6% were obese. The most common cancers were gastrointestinal (26.1%), lung (20.5%), and leukemia (12.1%).

There were 17,417 patients who received chemotherapy, 2319 who received immunotherapy, and 3560 who received targeted therapy. Approximately 65% of patients experienced 1 or more grade 3 or higher AE.

For each treatment domain, women experienced an increased risk of severe toxicity compared with men, with a 49% higher risk among those receiving immunotherapy (OR, 1.49; 95% CI, 1.24-1.78; P <.001).

For all treatments, women had a 25% higher risk of experiencing 5 or more severe AEs (OR, 1.25; 95% CI, 1.18-1.32; P <.001), with the strongest association seen for women receiving immunotherapy (OR, 1.42; 95% CI, 1.14-1.77; P <.001) or targeted therapy (OR, 1.50; 95% CI, 1.27-1.78; P <.001).

The researchers also found that women had a higher risk of symptomatic (OR, 1.33; 95% CI, 1.26-1.41; P <.001) and hematologic (OR, 1.30; 95% CI, 1.23-1.37; P <.001) AEs, with a similar pattern among those who received immunotherapy (OR, 1.66; 95% CI, 1.37-2.01; P <.001). There were no significant sex differences in the risk of nonhematologic AEs.

Among patients treated with immunotherapy, the risk of symptomatic AEs was higher in women receiving immune checkpoint inhibitors (OR, 1.54; 95% CI, 1.05-2.26; P =.03) and immune system modulators (OR, 1.62; 95% CI, 1.27-2.06; P <.001). This association was not observed for nonsymptomatic AEs.

According to the researchers, the greater severity of both symptomatic AEs and hematologic AEs in women across multiple treatment modalities points to broad sex differences in AEs. This may be attributed to several factors, including pharmacogenomics of drug metabolism or disposition, total dose received, and/or adherence to therapy.

The overall findings support the notion that sex differences may independently modulate drug toxicity. “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),” the researchers wrote.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Unger JM, Vaidya R, Albain KS, et al. Sex differences in risk of severe adverse events in patients receiving immunotherapy, targeted therapy, or chemotherapy in cancer clinical trials. J Clin Oncol. Published online February 4, 2022. doi:10.1200/JCO.21.02377