Under-representation of women in Randomized Clinical Trials testing anticancer immunotherapy may undermine female patients care. A call to action

Abstract

Immunotherapy with immune-checkpoint inhibitors (ICIs) has revolutionized the landscape of cancer treatment, dramatically improving the prognosis of patients with several solid tumors. Sex and gender are variables that affect immune responses to both foreign and self-antigens and growing preclinical and clinical evidence show that they also affect efficacy and tolerability of anticancer immunotherapy in patients with several advanced solid tumors. Despite such strong biological rationale and available evidence highlighting the need to take into account sex-based differences in the context of both research and clinical practice for anticancer immunotherapy, we described here an impressive under-representation of women enrolled in randomized clinical trials (RCTs) testing such drugs over the last 10 years. We critically discuss limitations the under-representation of women has on the generalization of results of RCTs to female patients, as well as the importance in the future of ensuring increased enrollment of women in trials, including sex as stratifying factor in trials design, and guaranteeing sex-specific analysis of efficacy and safety results, in order to avoid less than optimal treatment of women with cancer.