Assessing treatment outcomes of enfortumab vedotin dose reduction in metastatic bladder cancer.

4576 Background: Enfortumab Vedotin (EV), an antibody drug conjugate targeting Nectin-4, has emerged as first-line treatment for advanced Urothelial Carcinoma (UC) in combination with pembrolizumab. Acute and cumulative toxicity due to EV can adversely impact quality of life. Treatment related adverse events (TRAEs) are managed with dose and schedule modifications. Current treatment paradigm is to treat until unacceptable toxicity or progression. Our single center, retrospective study, aims to assess the impact of EV dose reduction on treatment duration, AEs, and survival. Methods: We conducted a retrospective analysis of patients with UC treated with EV +/- pembrolizumab. Patients were divided into 3 groups: A) 1.25 mg/kg dose and not dose-reduced; B) 1.25 mg/kg dose and dose-reduced; C) EV < 1.25 mg/kg. Data was collected from the EMR and we evaluated OS, PFS, TRAEs, and number of doses received. Kaplan Meier and Cox proportional hazards regression models were used to compare PFS and OS between the 3 groups, and to evaluate treatment dose (1.25 mg or <1.25 mg) as a time-varying covariate. TRAEs (y/n) and number of doses received were examined using logistic and negative binomial regression respectively. Regression models adjusted for age, ECOG status, and receipt of concurrent pembrolizumab. Results: 153 patients comprised the 3 groups: A) n= 47; B) n=73; C) n=33. The cohort was majority male (78.4%) and white (79.1%) with no significant difference across groups. Median age and ECOG score were both significantly higher in group C (p<0.001 and p=0.033, respectively). Overall, 52.9% of patients received prior immunotherapy, while 35.9% of patients received concurrent pembrolizumab (similar across groups). Patients started on full dose EV then reduced (B) had significantly more TRAEs than groups A and C (Neuropathy; A: 15.2%, B:34.2%, C: 12.1%, p<0.001; Cutaneous AE; A: 4.3%, B:27.4%, C:2.1%, p=0.004). In unadjusted Kaplan Meier analyses (months), there was a trend but no statistically significant difference in PFS (A:6.4, B:10.1, C:13.1; p=0.1) or OS (A:10.5, B:15.6, C:22.9; p=0.22). In adjusted analyses (minimum 5 doses of EV), there was no difference in total doses received across groups(p=0.6867). Adjusted Cox proportional hazards regression (HR) showed significantly improved PFS and OS for the dose-reduced groups by both landmark (Table 1) and time-covarying analyses (<1.25 PFS, HR: 0.6 p=0.032; <1.25 OS, HR: 0.59 p=0.039). Conclusions: In adjusted analyses dose reduced groups had significantly improved PFS and OS. These results suggest that changes in dose can decrease overall AEs while maintaining efficacy, warranting prospective evaluation. 1.25 mg/kg dose and dose-reduced Significance Started < 1.25 mg/kg Significance Landmark Analyses PFS (HR) 0.48 p=0.019 0.44 p=0.049 Landmark Analyses OS (HR) 0.53 p=0.038 0.47 p=0.063