Enfortumab vedotin treatment regimens and efficacy in urothelial carcinoma: The Mayo Clinic experience.
Authors: Ballouz Tara , Tripathi Nikita , Naqvi Syed Arsalan Ahmed , Saxena Akshat , Bibi Arifa , Kase Adam McLain , Childs Daniel S , Orme Jacob , Bryce Alan Haruo , Riaz Irbaz Bin , Singh Parminder 
Published: January 2024

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Background: Enfortumab vedotin (EV) is an antibody-drug conjugate recently approved to treat locally advanced or metastatic bladder cancer (la/mUC). Initial trials have shown promising response to EV in advanced urothelial cancers (UC), where prognosis is currently poor. Here, we report real-world experience using EV at a tertiary center. Methods: This study reports treatment details and outcomes in 92 patients (pts) that received at least one complete cycle of EV monotherapy in treatment of la/mUC. Treatment details include intent of cycle duration, 21 days (treatment on days 1 and 8) or 28 days (treatment on days 1, 8 and 15), dose reductions, and median number of cycles completed. Interruptions in treatment are reported as intentional (i.e. holding EV after achieving positive response) or unintentional (i.e. secondary to drug toxicity or other delay). Image-based best clinical response consists of progressive disease (PD), stable (SD), partial (PR), complete response (CR), and not evaluable (NE). Clinical benefit rate (CBR) is defined as either SD, PR, and CR outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Results: Patients mean age was 71.1 years (IQR: 66.8 - 78), 72 (79.2%) are male and 20 (20.8%) female, 89 (96.7%) pts received EV in the setting of metastatic UC, 3 (3.3%) in locally advanced UC. 13 (13.5%) pts were previously chemotherapy exposed, 9 (9.8%) were immunotherapy exposed, 60 (65.2%) were both chemo and immunotherapy exposed, and 11 (12.0%) received EV first line. 46 (50%) pts underwent 21-day treatment cycles, and 46 underwent 28-day treatment cycles. The median number of EV cycles was 3 (range 1-16) in the overall cohort, 3 in the 21-day cycle group, and 4 in the 28-day cycle group. 50 (54.3%) pts required dose reductions secondary to toxicity. 11 (12.0%) pts had planned interruptions, and 33 (35.9%) had unplanned interruptions. Best clinical response consisted of 24 (26.0%) pts with PD, 12 (13.0%) with SD, 25 (27.2%) with PR, 17 (18.5%) with CR, and 14 (15.2%) NE. CBR was 54 (58.7%) in the overall sample. CBR in the 21-day and 28-day cycle groups was identical at 27 (29.3%). EV therapy was discontinued most for cancer progression (34, 37.0%), therapy toxicity (18, 19.6%), and pt death (12, 13.0%). In 13 (14.1%) pts therapy is still ongoing. 73 (76.0%) pts had mild to moderate toxicities, and 19 (19.7%) reported severe toxicities that required hospitalization. Median OS in the total cohort was 11.01 months (95% CI: 8.51-14.6). Median PFS is 5.49 months (95% CI: 4.60-8.19). Conclusions: Real-world utilization of EV showed significant heterogeneity in administration patterns (21 days vs 28 days) and across a range of settings (first line, chemo exposed, IO exposed, chemo and IO exposed). Although EV has high response rates, more than 3/4th of patients suffered mild to moderate toxicities and 1/5th required hospitalization.