Sex-related differences in the efficacy and toxicity of cancer treatments

Differences between the biological sexes have long been observed in cancer incidence and prevalence, and in treatment outcomes including efficacy and toxicity. Ideally, there should be sufficient information to improve the individualization of cancer treatment by incorporating sex into treatment decisions. Necessary information should include: the nature and source of these differences; whether inherent to the specific cancer (such as molecular profiles, metabolic behaviors, and immune responses); the pathophysiological mechanisms of the specific cancer; or the pharmacokinetic and pharmacodynamic profiles of different cancer drugs. The influence of gender, which is defined as the sociocultural construct that determines societal norms for males and females, should also be included in personalized decision-making. This review aimed to describe the current evidence on the impact of sex and gender on treatment effects, outcomes, and toxicity profiles in cancer patients. Data for the influence of gender were negligible, whereas clinical studies and meta-analyses in different cancer types have identified differences between males and females in the effectiveness on survival outcomes of immunotherapy, chemotherapy, targeted therapy, and radiotherapy. Similarly, toxicity profiles of different cancer treatments varied between sexes. Based on these observed differences, it seems clear that sex should be included as an important variable when individualizing treatment; however, more research into sex- and gender-related differences in cancer treatment efficacy and toxicity, and the causes for these differences, is required before this can be fully incorporated into individualized treatment programs in real-world clinical practice.