Enfortumab vedotin (EV) is approved for the treatment of metastatic urothelial carcinoma (mUC), as monotherapy or in combination with immune checkpoint inhibitors (ICIs), following the results of recent practice-changing clinical trials, such as EV-301 and EV-302. However, EV-301 included only patients with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0 or 1, while ECOG-PS 2 mUC patients were excluded.
In clinical settings, the benefit of EV for this group of vulnerable patients remains a significant and yet unresolved question. The aim of our study was to evaluate the impact of ECOG-PS on survival outcomes in patients treated with EV using the ARON global real-world database.
A total of 483 mUC patients with ECOG-PS 0-1 and 85 with ECOG-PS 2 and treated with EV were included. The coprimary endpoints were Overall Survival (OS) and Progression-Free Survival (PFS) to compare the clinical outcomes of mUC patients with ECOG-PS 2 versus ECOG-PS 0 or 1. The secondary endpoints included the comparison of OS and PFS in these two patient groups according to metastatic sites (liver, bone, lung, lymph nodes, brain, soft tissue).
The median OS was 13.63 months (95% CI 11.9-15.57) and 6.34 months (95% CI 4.96-8.48) in mUC patients with ECOG-PS 0-1 and ECOG-PS 2, respectively. Patients with ECOG-PS 2 receiving EV reported statistically significantly shorter OS compared to those with ECOG-PS 0-1 (HR 2.24; 95% CI 1.64-3.06; p < 0.001). The median PFS was 7.39 months (95% CI 6.60-8.04) and 3.98 months (95% CI 3.21-5.95) in mUC patients with ECOG-PS 0-1 and ECOG-PS 2, respectively. Patients with ECOG-PS 2 receiving EV reported statistically significantly shorter PFS compared to those with ECOG-PS 0-1 (HR 1.71; 95% CI 1.29-2.27; p < 0.001). Similarly, shorter OS and PFS was observed in ECOG-PS 2 patients with liver, bone, lung, and lymph nodes metastases, while shorter PFS was associated with lymph nodes and bone metastases.
Our analysis showed worse survival outcomes in pretreated mUC with ECOG-PS 2 receiving EV monotherapy; however, given the retrospective design and baseline imbalances between ECOG groups, these findings should not be interpreted as evidence of reduced intrinsic EV efficacy. The outcomes of EV monotherapy in ECOG-PS 2 patients remains uncertain and can only be inferred from non-randomized prospective trials and studies based on real-world evidence. Further studies and multicentric translational collaborations are fundamental to validate these findings.
BMC cancer. 2026 Apr 30 [Epub ahead of print]
Alessandro Rizzo, Francesco Ciccimarra, Stenio de Casio Zequi, Samantha Bove, Maria Colomba Comes, Ondřej Fiala, Akihiro Yano, Kirstin Binz, Ray Manneh Kopp, Jawaher Ansari, Renate Pichler, Oronzo Brunetti, Daniele Santini, Alina Pirstuk, Annarita Fanizzi, Gerardo Cazzato, Mario Della Mura, Mobin Safi, Alvaro Pinto, Alessia Mennitto, Raffaella Massafra, Veronica Mollica, Yüksel Ürün, Matteo Rosellini, Matteo Santoni, Francesco Massari
1S.S.D. C.O.r.O. Bed Management Presa in Carico, TDM, IRCCS Istituto Tumori Giovanni Paolo II, Viale Orazio Flacco 65, Bari, 70124, Italy. ., 1S.S.D. C.O.r.O. Bed Management Presa in Carico, TDM, IRCCS Istituto Tumori Giovanni Paolo II, Viale Orazio Flacco 65, Bari, 70124, Italy., Department of Urology, A. C. Camargo Cancer Center, São Paulo, Brazil./National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation, A.C. Camargo Cancer Center, Sao Paulo, Brazil., Laboratorio di Bioinformatica e Biostatistica, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy., Department of Oncology and Radiotherapeutics, Faculty of Medicine, University Hospital in Pilsen, Charles University, Pilsen, Czech Republic., Department of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan., Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, Kansas City, US., Clinical Oncology, Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia., Medical Oncology, Tawam Hospital, Al Ain, UAE., Department of Urology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria., Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I, University of Rome, Rome, Italy., Department of Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic., Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Pathology Unit, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, Bari, 70124, Italy., U.O. Oncologia, Ospedale C. Urbani, Jesi, Italy., Department of Medical Oncology, Hospital Universitario La Paz, Madrid, Spain., Department of Medical Oncology, Azienda Ospedaliera Universitaria "Maggiore Della Carit", Novara, Italy., Scientific Directorate, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori "Giovanni Paolo II", Bari, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Department of Medical Oncology, Ankara University Faculty of Medicine, Ankara, 06620, Turkey., Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy., Oncology Unit, Macerata Hospital, Macerata, Italy.