Sex influence on cancer immunotherapy efficacy and safety in advanced non-small cell lung cancer (NSCLC): A Canadian institution real-world experience.

e20618 Background: Males and females differ in innate and adaptive immune responses. This difference may also be reflected in their response to cancer immunotherapies. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced NSCLC, however the impact of sex on treatment outcomes in these patients remains unclear. The aim of this retrospective cohort study was to evaluate sex-related differences in immunotherapy outcome in a real-world population of NSCLC patients treated with ICIs. Methods: Demographics, clinical, pathological and treatment characteristics were assessed. Treatment-related variables were analyzed to understand the differences in efficacy and safety outcomes including response rates, PFS, OS and all-cause treatment discontinuation (TD) in relation to sex. Results: 152 advanced NSCLC patients receiving first-line immunotherapy, either alone or in conjunction with chemotherapy, were included in the study cohort. Females were younger age, were more likely to be non-smokers, have non-squamous tumors and had a higher prevalence of pre-existing autoimmune diseases compared to males. Disease control (CR/PR/SD) was achieved in 65.8% of patients. Median PFS was 12.0 mo in females and 14.1 mo in males. Median OS for all patients was 15.8 mo; 16.1 and 15.7 mo in females and males respectively. No statistical differences based on gender were observed in PFS and OS (P = 0.767 and P = 0.657). In regression analysis older age and presence of liver metastases were independent poor prognostic factors. Gender was not an independent prognostic factor in PFS and OS. Notably, 44 or 28.9% patients developed symptomatic immune-related adverse events (ir-AEs) that led to TD (Table 1). ir-AE-related TD occurred at a significantly higher rate in females compared with males (Table 1; 38.2% vs 19.7%, RR = 1.90; 95% CI: 1.12 to 3.26; p = 0.018). GI toxicity, including hepatitis and colitis was predominantly observed in females, whereas pneumonitis was the most frequent ir-AE leading to TD in males. Conclusions: Despite no significant differences based on gender were observed in PFS and OS, our study showed that female patients with advanced NSCLC receiving ICIs are at a substantially greater risk of severe symptomatic ir-AEs and TD. This finding indicates that broad-based sex differences in this context could potentially exist and emphasizes the need for further investigations into the role played by gender in immunity and cancer immunotherapy treatment.Table: see text