ASCO GU 2024: Safety and Efficacy of Enfortumab Vedotin in Patients with Metastatic/locally Advanced Urothelial Cancer: Real-World Evidence from a European Database

( The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA was host to a urothelial carcinoma poster session. Dr. Stefanie Zschaebitz presented the results of a European real-world analysis of the safety and efficacy of enfortumab vedotin (EV) in patients with metastatic/locally advanced urothelial cancer.

EV is an antibody-drug conjugate consisting of a fully humanized monoclonal antibody directed against the extracellular domain of Nectin-4, conjugated to a microtubule-disrupting agent, monomethyl auristatin E (MMAE) via a protease-cleavable linker. EV is approved as a single agent treatment option for metastatic urothelial carcinoma patients with disease progression following platinum-based chemotherapy and immunotherapy (EV-301)1 and in combination with pembrolizumab for patients with locally advanced/metastatic urothelial carcinoma, irrespective of cisplatin eligibility.2 The most common and relevant adverse events with EV are neurotoxicity, dermatologic toxicity/pruritis, and fatigue. Adverse events of special interest include hyperglycemia, ophthalmologic toxicity, and pneumonia/interstitial disease. In this study, the authors report the updated efficacy and safety data of EV in a large European cohort of real-world patients (GUARDIANS) treated in hospitals and private practices. 

This was a retrospective analysis from 25 German and Swiss hospitals and private practices where patients received EV. Adverse events were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 0. Objective responses were evaluated by local investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Statistical analyses were conducted using the SPSS software.

This study cohort included 188 patients, with a median age of 66 years. 70% of patients had ECOG performance status of 0 – 1. EV was administered in the ≥4th line in 43% of patients. The baseline patient characteristics are summarized below: 


The median follow-up was 11 months (IQR: 6 – 17 months). The overall response rate was 46% (partial: 42% and complete: 4%), with a disease control rate of 58%. The median OS was 12 months, and the median PFS was 7 months. 


Any-grade adverse events were observed in 71% and CTCAE grade ≥3 in 32%. The most common any grade adverse events were:

  • Peripheral sensory neuropathy (33.5%)
  • Skin toxicity (25%)
  • Fatigue (23%) 


More frequent any grade toxicity was observed in patients ≥75 years of age. There were no age or sex differences with respect to median OS, PFS, ORR, or grade ≥3 adverse events.


Dr. Zschaebitz noted that future research needs to focus on the detection of biomarkers that predict response to treatment and toxicity to EV and mechanisms of resistance. The efficacy and toxicity of combination EV + pembrolizumab needs to also be evaluated in real-world populations.

Presented by: Stefanie Zschaebitz, MD, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024 


  1. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med 2021 Mar 25;384(12):1125-1135.
  2. FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. Accessed on January 26, 2024.