Real-world enfortumab vedotin +/- pembrolizumab (EV+/-P)–based treatment toxicity, treatment discontinuation, and associations with survival in advanced urothelial carcinoma (aUC).

4562 Background: EV-based therapy is central to the standard of care for aUC, increasingly in combination with P. Current understanding of EV-related toxicity is limited to clinical trial data. Here, we use real-world data to characterize the frequency of EV-based treatment-toxicity, -discontinuation, and associations with survival. Methods: We performed a post-marketing retrospective cohort study of EV+/-P initiators at the University of Pennsylvania (1/2020-5/2024). The frequency of any of five toxicities (skin reaction, neuropathy, ocular disorder, hyperglycemia, and pneumonitis) and associated treatment-interruptions (hold or discontinuation), -reduction, or -hospitalization were summarized. Among pts with at ≥1 year of follow-up, overall survival (mOS) was compared between pts with vs without each toxicity via KM methods. Results: Among 123 EV/EV+P treated pts, median age was 68 years, 72% were male, 74% were white, 68% had bladder primary, and 71% treated with EV alone. Frequency of toxicity, time to toxicity, and proportions requiring dose interruption, reduction, and hospitalization are shown (Table). 60% of pts had skin reaction, 47% neuropathy, 28% ocular disorder, 14% hyperglycemia, and 2% pneumonitis; treatment discontinuation occurred among 20% of pts with neuropathy, 5% of those with skin reaction, 3% of those with ocular disorders, and 0% of those with hyperglycemia or pneumonitis. Among 80 pts with at least one-year of follow-up (89% EV monotherapy), mOS was 14.3 months (95% CI: 11.3-19.3). Survival was greater among those with skin reaction, neuropathy, and ocular disorders (mOS skin reaction vs. no reaction: 19.3 vs. 6.4 months, p < 0.001; neuropathy vs. no neuropathy: 16.5 vs. 8.2 months, p = 0.001; ocular disorder vs. no ocular disorder: 17.1 vs. 11.3 months; p = 0.001). Conclusions: EV+/-P treatment toxicity occurred in a majority of pts, but treatment discontinuation was infrequent. Presence of toxicity was significantly associated with improved survival. Future work is needed to prospectively validate these findings. EV+/-P treatment toxicity and survival outcomes (n=123). Toxicity n (% of total) Months to Occurrence, Median (range) Dose Held*,n (%) Dose Reduced*,n (%) Discontinuation*n (%) Hospitalization*n (%) mOS**(n=80) Skin Reaction 74 (60) 0.7 (0.1-13.8) 33 (46) 33 (46) 4 (5) 4 (5) 19. 3 vs 6.4 (p<0.001) Neuropathy 58 (47) 2.9 (0.2-9.6) 28 (48) 23 (40) 11 (20) 0 (0) 16.5 vs. 8.2 (p=0.001) Ocular Disorder 35 (28) 1.8 (0.2-10.6) 4 (11) 3 (9) 1 (3) 0 (0) 17.1 vs 11.3 (p=0.001) Hyperglycemia 17 (14) 1.4 (0.1-5.6) 5 (29) 0 (0) 0 (0) 0 (0) 9.7 vs. 14.4 (p=0.56) Pneumonitis 3 (2) 3.8 (3.0-11.0) 1 (33) 0 (0) 0 (0) 1 (33) 22.1 vs. 14.3 (p=0.91) *n (% of pts w/ toxicity). **w/ vs w/o toxicity.