In a study reported in the Journal of Clinical Oncology, Joseph M. Unger, PhD, and colleagues found that women in clinical trials of chemotherapy, immunotherapy, or targeted therapy had a significantly greater risk for severe adverse events overall—and, particularly, with immunotherapy.

As stated by the investigators, “Women have more adverse events from chemotherapy than men, but few studies have investigated sex differences in immune or targeted therapies.”

Joseph M. Unger, PhD

Study Details

The study involved data from SWOG phase II and III clinical trials conducted between 1980 and 2019, excluding those in sex-specific cancers. A total of 27 adverse event categories were included in the analysis. Symptomatic adverse events were defined as those aligned with the National Cancer Institute’s Patient-Reported Outcome–Common Terminology Criteria for Adverse Events. Analyses were adjusted for age, race, and disease prognosis.

The study population (n = 23,296) included 8,838 women and 14,458 men from 202 trials who experienced a total of 274,688 treatment-related adverse events. Among the patients, 17,417 received chemotherapy (6,642 women and 10,775 men), 2,319 received immunotherapy (843 women and 1,476 men), and 3,560 received targeted therapy (1,353 women and 2,207 men).

Key Findings

Overall, 15,051 patients (64.6%) had at least one grade ≥ 3 (severe) treatment-related adverse event.

Overall, women were more likely to have a grade ≥ 3 adverse event (68.6% vs 62.2%, odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.27–1.42, P < .001). Risk was higher for women vs men among those receiving chemotherapy (73.9% vs 67.6%, OR = 1.36, 95% CI = 1.27–1.45, P < .001), immunotherapy (56.6% vs 48.8%, OR = 1.49, 95% CI = 1.24–1.78, P < .001), and targeted therapy (50.0% vs 44.8%, OR = 1.25, 95% CI = 1.09–1.44, P = .001).

Women were at increased risk of severe symptomatic adverse events overall (33.3% vs 27.9%, OR = 1.33, 95% CI = 1.26–1.41, P < .001), with the difference in risk being greatest among patients receiving immunotherapy (33.7% vs 25.4%, OR = 1.66, 95% CI = 1.37–2.01, P < .001).

Women were at increased risk of grade ≥ 3 hematologic adverse events (45.2% vs 39.1%, OR = 1.30, 95% CI = 1.23–1.37, P < .001). Risks for women were significantly increased among patients receiving chemotherapy (54.6% vs 47.7%, OR = 1.32, 95% CI = 1.24–1.4, P < .001) and those receiving immunotherapy (22.1% vs 18.4%, OR = 1.32, 95% CI = 1.06–1.65, P = .013).

The risk of grade ≥ 3 nonhematologic adverse events was greater among women overall (30.9% vs 29.0%, OR = 1.08, 95% CI = 1.02–1.14, P =.01), with no significant between-sex differences observed according to treatment type.

The investigators concluded, “The greater severity of both symptomatic adverse events and hematologic adverse events in women across multiple treatment modalities indicates that broad-based sex differences exist. This could be due to differences in adverse events reported, pharmacogenomics of drug metabolism/disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving immunotherapy, suggesting that studying adverse events from these agents is a priority.”

Dr. Unger, of the SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Institutes of Health, National Cancer Institute, and National Cancer Trials Network. For full disclosures of the study authors, visit ascopubs.org.