This exploratory analysis evaluated efficacy and safety data for enfortumab vedotin versus chemotherapy over median follow-up of approximately 2 years from EV-301.
Patients with locally advanced/metastatic urothelial carcinoma with prior platinum-containing chemotherapy and disease progression during/after programmed cell death protein 1/ligand 1 inhibitor treatment were randomized to enfortumab vedotin or chemotherapy (docetaxel, paclitaxel, vinflunine).
Endpoints were overall survival (primary), progression-free survival (PFS), objective response, and safety.
In total, 608 patients were included (enfortumab vedotin, n = 301; chemotherapy, n = 307). With median follow-up of 23.75 months, 444 deaths had occurred (enfortumab vedotin, n = 207; chemotherapy, n = 237). Risk of death was reduced by 30% with enfortumab vedotin versus chemotherapy (HR 0.70 [95% CI, 0.58 to 0.85]; 1-sided, log-rank P = 0.00015); PFS improved with enfortumab vedotin (HR 0.63 [95% CI, 0.53 to 0.76]; 1-sided, log-rank P < 0.00001). Treatment-related adverse event rates were 93.9% for enfortumab vedotin and 91.8% for chemotherapy; grade ≥ 3 event rates were 52.4% and 50.5%, respectively. Grade ≥ 3 treatment-related decreased neutrophil count (14.1% vs 6.1%), decreased white blood cell count (7.2% vs 1.4%), and anemia (7.9% vs 2.7%) were more common with chemotherapy versus enfortumab vedotin; maculopapular rash (7.4% vs 0%), fatigue (6.8% vs 4.5%), and peripheral sensory neuropathy (5.1% vs 2.1%) were more common with enfortumab vedotin. Of special interest adverse events, treatment-related skin reactions occurred in 47.3% of patients receiving enfortumab vedotin and 15.8% of patients receiving chemotherapy; peripheral neuropathy occurred in 48.0% versus 31.6%, respectively, and hyperglycemia in 6.8% versus 0.3%.
After median follow-up of approximately 2 years, enfortumab vedotin maintained clinically meaningful overall survival benefit versus chemotherapy, consistent with findings from the EV-301 primary analysis; PFS and overall response benefit remained consistent. Adverse events were manageable; no new safety signals were observed.
Annals of oncology : official journal of the European Society for Medical Oncology. 2023 Sep 05 [Epub ahead of print]
J E Rosenberg, T Powles, G P Sonpavde, Y Loriot, I Duran, J-L Lee, N Matsubara, C Vulsteke, D Castellano, R Mamtani, C Wu, M Matsangou, M Campbell, D P Petrylak
Department of Medicine, Division of Solid Tumor Oncology, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY., Department of Genitourinary Oncology, Barts Cancer Institute, CRUK Experimental Cancer Medicine Centre, London, UK., Department of Bladder Cancer, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA., Department of Renal Cancer, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Department of Medical Oncology, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain., Department of Oncology, Urologic Cancer center, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea., Department of Breast and Medical Oncology, National Cancer Center Hospital East, Chiba, Japan., Department of Molecular Imaging - Pathology - Radiotherapy - Oncology, Center for Oncological Research (CORE), University of Antwerp, Integrated Cancer Center Ghent, Ghent, Belgium., Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA., Department of Biostatistics, Astellas Pharma, Inc., Northbrook, IL., Department of Therapeutic Area-Oncology, Astellas Pharma, Inc., Northbrook, IL., Department of Late Stage Development, Seagen Inc., Bothell, WA., Department of Medicine and Urology, Yale Cancer Center, New Haven, CT. Electronic address: .