Real-world evidence for enfortumab vedotin (EV) in metastatic urothelial carcinoma (mUC): a multi-centred observational study in a publicly funded Canadian system.
Authors: Peng Jenny , Hueniken Katrina , Proulx-Rocray Francis , Alimohamed Nimira S. , Fallah-rad Nazanin , Kumar Vikaash , Al-Ezzi Esmail M. , Jiang Di (Maria) , Blais Normand , Sridhar Srikala S. 
Published: June 2024

e16566 Background: EV is a life-prolonging antibody drug conjugate approved and funded in Canada for use in patients with mUC after platinum-based chemotherapy and immune checkpoint inhibitors (ICI). Recently, EV has shown comparable real-world results in the US, Germany, and Switzerland, utilizing a mixed public and private payer system. We report here real-world outcomes associated with EV monotherapy in mUC patients in Canada. Methods: Following ethics approval, a retrospective chart review was conducted for patients with unresectable locally advanced or mUC who initiated EV monotherapy between January 2021 and August 2023 across 3 large academic centres in Canada (Toronto, Calgary, and Montreal). Efficacy was assessed by response rate (RR), progression free survival (PFS), and overall survival (OS) gathered from electronic medical records. Kaplan-Meier curves and logrank tests were used to characterize survival outcomes, Chi-square and Fisher's exact were used to evaluate response rates. Results: Fifty one patients were identified. They were mostly male (n=47, 92%) with a median age of 70 (37 to 89) and had an ECOG performance status of 0 to 1 (n=40, 78%). Primary tumor site included bladder (n=28, 55%), upper tract (n=19, 37%), urethral (n=3, 6%), or unknown (n=1, 2%). Sites of metastases included lymph nodes (n=38, 75%), lung (n=22, 43%), liver (n=16, 31%), and bone (n=24, 47%). Median follow-up was 14.2 (2.6 to 25.8) months. On average, patients received 5.4 (IQR 2.7 to 8.4) months of EV. The RR was 49%, median PFS was 7.6 months (95% CI 5.4 to 12.7) and median OS was 16.1 months (95% CI 9.8 to not reached). Although PFS was improved among younger patients <=75 years old (p=0.04), OS was similar regardless of age (p=0.76). No significant differences in PFS or OS were found based on site of metastases or prior use of cisplatin versus carboplatin. Higher Bellmunt risk criteria was strongly associated with shorter OS (p=0.012). Most frequent toxicities were fatigue (n=27, 53%), rash (n=21, 41%), and peripheral neuropathy (n= 17, 33%); higher rates of peripheral neuropathy were associated with treatment response (p=0.007). Several patients required dose reductions (n=32, 63%) or interruption (n=42, 82%). Fourteen patients (27%) received subsequent therapy following EV, including paclitaxel (n=7), platinum-rechallenge (n=3), pembrolizumab (n=2), sacituzumab govitecan (n=1), and erdafitinib (n=1). Conclusions: Canadian patients treated with EV monotherapy experienced similar PFS and OS to those reported in clinical trials. The Bellmunt risk score strongly predicted OS and peripheral neuropathy was associated with treatment response. These data strongly support the use of EV monotherapy in real-world settings, regardless of age, site of metastases, or cisplatin-eligibility.