Broad-based sex differences exist in the severity of side effects from cancer and its treatment, with female patients at an overall 34% higher risk for severe symptoms than male patients—and the risk jumps to nearly 50% for immunotherapies, researchers reported in the Journal of Clinical Oncology.

Using data from 202 Southwestern Oncology Group (SWOG) phase II and III clinical trials conducted from 1980–2019, researchers analyzed the incidence of treatment-related adverse events by sex across 23,296 patients. Those patients reported experiencing 274,688 adverse events: 17,417 with chemotherapy, 2,319 with immunotherapy, and 3,560 with targeted therapy.

Overall, 64.6% of the female patients experienced one or more grade 3 or higher adverse event, which translated to a 34% increased risk of severe adverse events compared with male patients. Their risk was higher across all of the treatment modalities, especially immunotherapy, and increased risk of severe hematologic adverse events was particularly associated with chemotherapy or immunotherapy.

“Understanding the mechanisms underlying sex differences could potentially lead to new ways of developing and delivering therapies that reduce toxicity, particularly among females,” the researchers said. “A patient’s sex has not really been considered a component of individualized approaches to cancer medicine. But if the new findings are confirmed by other groups, then perhaps patient sex should be considered.”