Enfortumab vedotin plus pembrolizumab in metastatic urothelial carcinoma: First results on outcomes and safety in a German multicenter real-world patient cohort (GUARDIANS).

715 Background: The prospective phase 3 study EV-302 demonstrated superiority regarding efficacy of Enfortumab vedotin plus Pembrolizumab (EVP) compared to platinum-based chemotherapy in patients (pts) that received first-line (1L) therapy for metastatic urothelial carcinoma (mUC). Since presentation of the data in September 2023 EVP was considered a new standard of care (SOC) however only approved in Europe in August 2024. We analyzed efficacy and safety outcomes of pts treated with EVP outside of clinical trials. Methods: Retrospective data were collected from 19 German academic and community hospitals for pts with metastatic UC who received EVP as off-label therapy when reimbursed by their insurance company before European Medicines Agency (EMA) approval, or as SOC treatment after EMA approval. Imaging and therapy management were in accordance with local standards. Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Median progression-free survival (mPFS) and overall survival (mOS) were estimated using the Kaplan-Meier method by local investigators. Results: We identified 215 pts for the safety cohort (all pts who received EVP at least once) and 164 pts for the efficacy cohort (all pts who received at least one staging or died prior to first planned imaging).The median age for the eligible patients was 71 yr (range 25-89). The Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2/3-4/unknown for 46.0/31.6/17.2/4.7/0.5% of patients. The overall response rate was 60.7% (partial response 51.0%, complete response 9.7%). mOS was not reached and mPFS was 13 mo (95% confidence interval 4.5-21.5). Any-grade AEs were observed in 73.0% and CTCAE grade ≥3 AEs in 30.2%. Any-grade immune-related AEs were observed in 37.7% and CTCAE grade ≥3 AEs in 16.7%. The most common AEs were peripheral sensory neuropathy (all grade: 30.2%) and skin toxicity (all grade:24.2%). No treatment-related fatal event occurred. Limitations include the retrospective design and short follow-up. Conclusions: Administration of EVP in a real-world patient population showed promising effectiveness and an acceptable toxicity profile. No new safety signals were reported. Our results support the use of EVP in 1L in pts with mUC. Updated data with longer follow-up will be presented at the meeting.