Gender matters. Sex-related differences in immunotherapy outcome in patients with non-small cell lung cancer

Background: Emerging evidence identified sex as a variable regulating immune system functions and modulating response to immunotherapy in cancer patients. Objective: This retrospective study analysed sex-related differences in immunotherapy outcomes in a real-world population of non-small cell lung cancer (NSCLC) patients treated with immune check point inhibitors (ICIs). Methods: We retrospectively investigated clinical data of 99 patients with advanced NSCLC and treated with single-agent nivolumab and pembrolizumab at Medical Oncology Unit, Careggi Universi ty Hospital, Florence (Italy), between April 2014 to August 2019. Main clinical characteristics and clinical outcomes were analysed. Results: Our study showed that the efficacy of ICI treatment differed according to gender. A trend for better median progression-free survival (mPFS) was reported in males (mPFS 5.0 months, 95% Con fidence Interval [CI] 4.0-11.0) than females (mPFS 4.5 months, 95% CI 2.0-9.0) (p=0.133), while no significant difference for overall survival (OS) between the two sex groups was observed (p=0.622). In the nivolumab cohort, we showed a statistically significant difference for a longer PFS in men compared to women (log-rank p=0.054), HR for PFS in females versus males was 1.81 (95% CI 0.97-3.37, p=0.062). Disease control rate (DCR) was achieved in 55.7% and 45.7% of men and women, respectively, while disease progression was registered in 44.3% of males and 54.3% of females (p=0.386). Conclusion: Gender is a variable that should be taken into account in the choice of immunotherapy. Future prospective randomized trials testing tailored sex-based immunotherapy strategies are required to validate our findings before integrating into clinical practice.