Curative-Intent Immunotherapy: Does Sex Matter, and Is Earlier Treatment Better?

Immune checkpoint inhibitors (ICIs) have transformed treatment for many cancers and are increasingly being used with curative intent in earlier-stage disease. However, two clinically important questions remain unresolved: whether treatment efficacy differs between women and men, and whether ICIs work better when given before surgery rather than only afterwards.

Sex-related differences in immune function, hormone biology, pharmacokinetics and tumour characteristics could theoretically influence immunotherapy response. Studies in patients with metastatic disease examined whether sex affects treatment outcomes, but findings were mixed, with some meta-analyses indicating possible sex-based differences in treatment efficacy. At the same time, neoadjuvant treatment—administered while the primary tumour remains in place—may enhance antitumour immunity by exposing the immune system to a larger reservoir of tumour antigens. Hollinger and colleagues therefore examined both sex and treatment timing across randomized phase 3 trials of curative-intent ICI therapy.