Neuropathy, skin rash, and hyperglycemia as predictors of response to enfortumab vedotin in locally advanced and metastatic bladder and upper tract urothelial carcinoma.

771 Background: Enfortumab vedotin (EV) in combination with pembrolizumab is FDA approved for treatment of locally advanced and metastatic urothelial cancer. Neuropathy, skin rash, and hyperglycemia are common side effects of EV. We evaluated the impact of presence of neuropathy, skin rash, and hyperglycemia on progression free survival (PFS) in patients (pts) with bladder or upper tract urothelial carcinoma treated with EV. Methods: The Indiana University bladder cancer database was queried for pts with locally advanced and metastatic bladder and upper tract urothelial carcinoma who were treated with EV with or without pembrolizumab. Pts with variant histology were included. Toxicities were documented throughout the course of treatment. Association of neuropathy, skin rash and hyperglycemia and PFS were compared to patients without any of the side effects using the log-rank test. Results: Between 2018-2024, a total of 83 pts were treated with EV with at least 2 doses. The median age was 69 years (range, 39-89). 47 pts had EV + pembrolizumab, while 36 pts had EV as single agent. 43 pts received EV as 1st, 28 pts as 2nd, 10 pts as 3rd, and 2 pts as 4th line of treatment. Metastatic sites were lymph nodes in 42 pts, lungs in 34 pts, bones in 29 pts, liver in 16 pts, and brain in 7 pts. Median follow-up from the start of EV treatment was 14 months (range, 1-33). Neuropathy was reported in 30 (36%) pts, skin rash in 32 (39%) pts, and hyperglycemia in 6 (7%) pts. The median PFS in patients who did not experience neuropathy/skin rash/hyperglycemia was 4.5 months (95% CI, 2.4-11.0), 10.6 months (95% CI, 7.2-15.7) in pts who experienced neuropathy (P = 0,01), 8.6 months (95% CI, 7.3-20.2) in pts who experienced skin rash (P = 0.01), and 15.9 months (95% CI, 5.1-15.9) in pts who experienced hyperglycemia (P = 0.03). Conclusions: The presence of neuropathy, skin rash, or hyperglycemia in patients with metastatic bladder or upper tract urothelial carcinoma treated with EV was associated with improved PFS.