Side effects in oncology: Why does gender matter?

Women and men differ in the type and severity of side effects during chemotherapy. Few studies have investigated gender-specific reactions to other tumour treatments such as immunotherapies.

30 years of data on side effects and more than 200 studies

A recent study in the United States looked for the first time at the gender-related differences in the frequency and severity of side effects after immunotherapy or targeted tumour therapy. In total, the study included data from 23,296 patients from 202 studies between 1989 and 2019. The data were from 8,838 female patients and 14,458 male patients.

Of the patients in the study, 17,417 received chemotherapy, 2,319 received immunotherapy and another 3,560 received targeted therapy. In total, 274,688 adverse effects occurred across all treatments.

Women have a higher risk of serious side effects

In about 65% of all cases (n = 15,051), severe side effects of grade 3 or higher occurred in the course of treatment. Interestingly, women had a 34% higher risk (OR = 1.34; 95% CI: 1.27-1.42; P < 0.001) of serious side effects compared to men, including a 49% higher risk in the case of immunotherapies (OR = 1.49; 95% CI: 1.24-1.78; P < 0.001).

In addition, women had an increased risk of severe symptomatic side effects across all treatments, but especially so with immunotherapy (OR = 1.66; 95% CI: 1.37-2.01; P < 0.001). Also, women who received chemotherapy or immunotherapy experienced more severe haematological side effects. In contrast, there were no statistically significant gender differences for non-haematological side effects.

What do these findings mean in terms of oncology practice?

The increased risk of severe symptomatic and haematological side effects in women suggests that there are significant gender differences in the toxicity and effects of conservative oncological therapies.

Any such differences might affect pharmacokinetics, drug metabolism as well as dosages and treatment adherence. In particular, the strong gender differences and the associated side effects of modern immunotherapies in women call for closer attention in future studies. Until then, in therapy planning and risk counselling, men and women should be informed about these possible differences.

Source:
Unger JM 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 2022.