Survival disparities by sex with contemporary advanced urothelial carcinoma (aUC) therapy: A real-world analysis.

670 Background: Retrospective population data suggest poorer survival for female aUC patients. However, data on survival disparities in the era of immuno- and targeted therapies is limited. Methods: This cohort study used Flatiron Health’s nationwide de-identified electronic health record (EHR)-derived database. 7,244 patients (pts) were identified. Patients started on systemic therapy for aUC from 1/1/2017 to 5/1/2024, with reported sex, were included. Baseline demographics (including social determinants of health (SDOH) score), Eastern Cooperative Oncology Group performance status (ECOG PS), disease characteristics, treatment history, and clinical outcomes were abstracted. Progression free survival (PFS) and overall survival (OS) were compared between male and female patients, via Kaplan-Meier log-rank analysis and Cox proportional hazards models that included race, gender, and first-line therapy. Independent sample t-tests and chi-square analyses were used for univariate comparisons. P-values < 0.05 were considered statistically significant. Results: A total of 3,045 pts with aUC were identified. 762 were (25.0%) female. In 1L, 28% received immunotherapy (IO) monotherapy, 3.4% received enfortumab vedotin+pembrolizumab (EVP), 37% received carboplatin (carbo), 28% cisplatin (cis), and 6% other chemotherapy (p=0.814). Females were more like to have ECOG PS>1 at diagnosis (p=0.020). Greater SDOH score was not associated with sex (p>0.1). Female sex was associated with inferior 1L PFS (median 4.3 vs 4.6m; HR 1.14, p=0.04) but no difference in OS (6.4 vs 6.5m; HR 1.01, p=0.2). Females had inferior PFS to men on Cox multivariable analysis when adjusting for race and first line therapy (p=0.006). On Cox univariate analysis stratified by 1L treatment, PFS was comparable between sexes on carbo (n=1127; p=0.4), cis (n=856; p=0.2) and EVP (n=25, p= 0.7), but women had inferior PFS to men on IO (n=595, p= 0.01). Women had comparable OS to men among all 1L treatments. Conclusions: In a large real-world database, female aUC patients had inferior PFS but comparable OS to males. Among 1L treatments, only immunotherapy was associated with inferior PFS for females vs. males. Baseline characteristics and survival in males vs. females. Male (n=2283) Female (n=762) Sig (p) Baseline Characteristics ECOG PS 0-1 (%) 64.1 60.6 0.020 2-4 (%) 15.2 17.8 Treatment at Academic Center (%) 19.1 18.0 0.360 SDOH score 3.13 3.07 0.110 1L Treatment IO (%) 27.7 28.1 0.814 EVP (%) 3.3 3.7 Carbo (%) 37.3 36.2 Cis (%) 27.5 28.9 Other (%) 6.6 6.1 Survival mPFS (m) 4.6 4.3 0.040 mOS (m) 6.5 6.4 0.200 Sig. values in bold (p<0.05).