e16562 Background: Enfortumab vedotin (EV) is an antibody drug conjugate targeting Nectin-4. It was approved by EMA/FDA in patients (pts) with metastatic/ locally advanced urothelial cancer post platinum and immune check point inhibitors (ICI) following the results of the EV-301 trial. We report updated efficacy data of EV in a large European cohort of real-world pts (GUARDIANS consortium) treated in hospitals and private practices. Methods: Retrospective data were collected from 25 German and Swiss hospitals and private practices for pts who received EV. Objective responses were evaluated by local investigators according to Response Evaluation Criteria in Solid Tumors version 1.1. Cox proportional hazard model was used to analyze risk patterns. Correlation was assessed using spearmen’s rank correlation coefficient. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: We identified 188 pts (32.4% female) with a median age of 66 yrs (range 31-89; 22.3% ≥ 75 yrs). Median OS (mOS) was 12.0 months (mo) (95% CI 9.65-14.35) and median PFS (mPFS) was 7.0 mo (95% CI 5.43-8.57). Overall response rate was 46.3% (partial remission: 42.0%, complete response 4.3%). Median follow up was 11 mo (IQR: 6.0-17.0 mo). Eastern Cooperative Oncology Group performance status (ECOG PS) was 0-1/ 2-4/ unknown in 75/14/11%. With decreasing ECOG-PS ≥2, there was also a decrease in OS 4.95 (95 CI 3.0-8.3; p<0.001) and PFS 2.1 (95 CI 1.14-3.92), resulting in a significant Spearman coefficant for death 0.31, OS -0.36 and PFS -0.31 (p<0.001). Median EV line was 3 (IQR: 3-4). Bellmunt Risk Score (BRS) >1 prior to EV initiation significantly predicts poorer OS and PFS with 3.3 (95 CI 1.82-5.72, p<0.001) and 1.9 (65 CI 1.15-3.25, p=0.013), respectively. Regarding metastases localization, liver and bone involvement correlated with poorer OS with 1.3 (95 CI 0.9-2.1; p=0.01) and 1.5 (95 CI 1.01-2.36; p=0.04). In addition cancer of the Upper Urinary Tract showed a poorer OS 1.4 (95 CI 0.89-2.19; p=0.027). Prior definitive local intervention demonstrated improvement in OS 0.6 (95 CI 0.32-1; p=0.048). Response to ICI-therapy, IC or CPS did influence neither OS nor PFS. Limitations are retrospective design and short follow-up. Conclusions: Anti-tumor activity of EV in real-world pts including difficult-to-treat subgroups is comparable to the results of the pivotal EV-301 trial. Frail pts. have a significant higher risk for death and progression. BRS is a predictive indicator for treatment with EV in heavily pretreated patients. Liver and bone metastases have a poorer OS. The improvement in prognosis after local definitive therapy in connection with EV therapy should be investigated further in the future.
