Sex-based differences in clinical outcomes of enfortumab vedotin and NECTIN-4 expression in urothelial cancer
Year: 2026
Type: article
Study design: Observational Study
Abstract: Sex-based differences in outcomes are well documented across tumor types and treatment modalities; however, it remains unclear whether these disparities extend to antibody-drug conjugates (ADCs). We report a retrospective, international real-world analysis of metastatic urothelial carcinoma (mUC) patients treated with Enfortumab Vedotin (EV), a NECTIN-4 ADC. Male patients demonstrate significantly longer median overall survival and time on treatment compared to female patients. Analysis of NECTIN-4 expression in urothelial cancer samples from the TCGA database reveals significantly higher expression in male patients’ tumors. This difference remains significant after adjusting for molecular subtype and is further modulated by smoking status and associates with estrogen pathway activity. These findings suggest that sex-related differences in target expression and hormonal signaling correlate with clinical outcomes of EV in mUC. Prospective studies should incorporate sex as a biological variable in ADC research to optimize treatment strategies for both male and female patients.
Source: Nature Communications
Authors: Tarek Taha, Ayelet Alpert, Jalal Baranseh, Alessandro Rizzo, Francesco Ciccimarra, Enrique Grande, Joaquim Bellmunt, Sebastiano Buti, Francesco Massari, Shilpa Gupta, Fernando Sabino Marques Monteiro, Ravindran Kanesvaran, Giandomenico Roviello, Cristian Lolli, Yüksel Ürün, Hideki Takeshita, Avivit Peer, Aristotelis Bamias, Matteo Santoni, Ithai Waldhorn
Institutions: Royal Marsden NHS Foundation Trust, Bar-Ilan University, Institute of Cancer Research, Rambam Health Care Campus, Istituto Tumori Bari, Universidad Francisco de Vitoria, Hospital Universitario Quirónsalud Madrid, IDCQ Hospitales y Sanidad, S.L.U., Harvard University, Dana-Farber Cancer Institute, University of Parma, University of Bologna, Cleveland Clinic, Hospital Sírio-Libanês, Latin American Cooperative Oncology Group (LACOG), National Cancer Centre Singapore, University of Florence, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Ankara University, Saitama Medical Center, Saitama Medical University, National and Kapodistrian University of Athens, University General Hospital Attikon, Ospedale di Macerata, ARON Research Foundation ETS, Technion – Israel Institute of Technology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7223888574