Community Oncology Research Program, Hope Foundation for Cancer Research, National Cancer Trials Network, NCI, NIH and Secondary Data Analysis grants supported the study. Unger reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Women demonstrated a 34% increased risk for severe adverse events from any cancer treatment compared with men, according to a study published in Journal of Clinical Oncology.
The risk appeared 49% higher among women vs. men who received immunotherapy, with differences especially apparent for symptomatic and hematologic adverse events.
Rationale and methods
“Although women have been identified as having more toxicity from chemotherapy treatments, almost no research has been done to evaluate whether women have more toxicity from newer, novel therapies, such as targeted therapy or immunotherapy for cancer,” Joseph M. Unger, PhD, SWOG Cancer Research Network health services researcher and biostatistician at Fred Hutchinson Cancer Research Center, told Healio.
Unger and colleagues assessed treatment-associated adverse events by sex among 23,296 individuals (62.1% men) included in 202 phase 2 and phase 3 SWOG clinical trials conducted between 1980 and 2019. They excluded trials involving sex-specific cancers.
Most patients received chemotherapy (n = 17,417), followed by targeted therapy (n = 3,560) and immunotherapy (n = 2,319).
Researchers used Common Terminology Criteria for Adverse Events to group adverse event codes and grade, and defined symptomatic adverse events as those aligned with NCI’s Patient-Reported Outcome-Common Terminology Criteria for Adverse Events. They assessed 13 symptomatic and 14 objective adverse event categories, and used multivariable logistic regression and adjusted for race, disease prognosis and age.
Overall, researchers analyzed 274,688 adverse events.
Results showed 64.6% of patients experienced one or more severe adverse events, with women experiencing a 34% increased risk for severe adverse events compared with men (68.6% vs. 62.2%; OR = 1.34; 95% CI, 1.27-1.42). This included a 49% increased risk among those treated with immunotherapy (OR = 1.49; 95% CI, 1.24-1.78).
Researchers observed an increased risk for severe symptomatic adverse events associated with all treatments among women, with a specific increase among women who received immunotherapy (OR = 1.66; 95% CI, 1.37-2.01).
Moreover, women treated with chemotherapy or immunotherapy experienced severe hematologic adverse events. Conversely, researchers did not observe significant sex differences in the risk for nonhematologic adverse events.
Joseph M. Unger
“Although prior studies had demonstrated that women have more toxicity from chemotherapy, almost no research evaluated whether women had more toxicity associated with novel new therapies,” Unger said. “The finding that women had a nearly 50% increased risk for severe toxicity compared with men from immunotherapy was especially dramatic and suggests further study about sex differences in this treatment domain is needed to validate these observations and identify mechanisms of increased risk.”
Future research should evaluate whether the adverse event patterns extend to patient reports of their quality of life, Unger said.
“This measure most clearly reflects the sense of wellbeing of patients, so identification of possible differences by sex could be very useful for patients and their physicians for guiding therapy,” he said.
For more information:
Joseph M. Unger, PhD, can be reached at Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, M3-C102, Seattle, WA 98109; email: firstname.lastname@example.org.