Sex-based differences in clinical outcomes of enfortumab vedotin and NECTIN-4 expression in urothelial cancer
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.
Related
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- Circulating Tumor DNA Clearance Is Associated with Response and Survival in Metastatic Urothelial Carcinoma Treated with First-Line Enfortumab Vedotin Plus Pembrolizumab
- Skin Toxic Effects and Survival With Enfortumab Vedotin-Pembrolizumab in Advanced Urothelial Carcinoma.
BibTeX
@article{taha2026sexbased,
title = {{Sex-based differences in clinical outcomes of enfortumab vedotin and NECTIN-4 expression in urothelial cancer}},
author = {Tarek Taha and Ayelet Alpert and Jalal Baranseh and Alessandro Rizzo and Francesco Ciccimarra and Enrique Grande and Joaquim Bellmunt and Sebastiano Buti and Francesco Massari and Shilpa Gupta and Fernando Sabino Marques Monteiro and Ravindran Kanesvaran and Giandomenico Roviello and Cristian Lolli and Yüksel Ürün and Hideki Takeshita and Avivit Peer and Aristotelis Bamias and Matteo Santoni and Ithai Waldhorn},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78988-7},
url = {https://www.nature.com/articles/s41467-026-78988-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sex-based differences in clinical outcomes of enfortumab vedotin and NECTIN-4 expression in urothelial cancer
AU - Tarek Taha
AU - Ayelet Alpert
AU - Jalal Baranseh
AU - Alessandro Rizzo
AU - Francesco Ciccimarra
AU - Enrique Grande
AU - Joaquim Bellmunt
AU - Sebastiano Buti
AU - Francesco Massari
AU - Shilpa Gupta
AU - Fernando Sabino Marques Monteiro
AU - Ravindran Kanesvaran
AU - Giandomenico Roviello
AU - Cristian Lolli
AU - Yüksel Ürün
AU - Hideki Takeshita
AU - Avivit Peer
AU - Aristotelis Bamias
AU - Matteo Santoni
AU - Ithai Waldhorn
PY - 2026
DA - 2026/10/27
JO - Nature Communications
DO - 10.1038/s41467-026-78988-7
UR - https://www.nature.com/articles/s41467-026-78988-7
AB - 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.
SN - 2041-1723
ER -