Toxicity, Dose Intensity, and Clinical Outcomes with First-Line Enfortumab Vedotin Plus Pembrolizumab in Advanced Urothelial Carcinoma: A Multicenter Real-World Study.
Enfortumab vedotin plus pembrolizumab (EVP) is the standard first-line treatment for locally advanced or metastatic urothelial carcinoma (la/mUC); however, real-world toxicity patterns, timing of onset, and prognostic significance of treatment-related adverse events (AEs) remain incompletely characterized.
We conducted a retrospective, multicenter analysis of 60 la/mUC patients treated with first-line EVP in Alberta, Canada (September 2024-January 2026). Treatment related toxicities, time to AE onset, dose modifications, and treatment discontinuation were assessed. Progression-free survival (PFS) and overall survival (OS) were analyzed.
The median age was 69 years, 82% of patients were male, and 80% had metastatic disease at treatment initiation. Histology was pure urothelial in 82% and mixed in 18%. Median follow-up was 10.3 months, and the median number of EV and pembrolizumab cycles was seven and eight, respectively. Rash (63%), fatigue (57%), and peripheral neuropathy (47%) were the most common adverse events, with median onset at 17, 29, and 90 days, respectively. Dose reductions occurred in 62%, dose delays in 43%, and treatment discontinuation in 38%. An initial enfortumab vedotin dose of 1.25 mg/kg was associated with improved PFS (HR 0.30, 95% CI 0.13-0.68; p = 0.004) and OS (HR 0.32, 95% CI 0.10-0.97; p = 0.044) compared with 1.0 mg/kg. Neuropathy was associated with improved PFS (HR 0.32, 95% CI 0.14-0.73; p = 0.007) and OS (HR 0.24, 95% CI 0.07-0.87; p = 0.029), while rash was associated with improved OS (HR 0.31, 95% CI 0.11-0.91; p = 0.032).
EVP was associated with frequent treatment-related adverse events requiring dose modifications, and the development of rash and peripheral neuropathy was associated with favorable survival outcomes.
We conducted a retrospective, multicenter analysis of 60 la/mUC patients treated with first-line EVP in Alberta, Canada (September 2024-January 2026). Treatment related toxicities, time to AE onset, dose modifications, and treatment discontinuation were assessed. Progression-free survival (PFS) and overall survival (OS) were analyzed.
The median age was 69 years, 82% of patients were male, and 80% had metastatic disease at treatment initiation. Histology was pure urothelial in 82% and mixed in 18%. Median follow-up was 10.3 months, and the median number of EV and pembrolizumab cycles was seven and eight, respectively. Rash (63%), fatigue (57%), and peripheral neuropathy (47%) were the most common adverse events, with median onset at 17, 29, and 90 days, respectively. Dose reductions occurred in 62%, dose delays in 43%, and treatment discontinuation in 38%. An initial enfortumab vedotin dose of 1.25 mg/kg was associated with improved PFS (HR 0.30, 95% CI 0.13-0.68; p = 0.004) and OS (HR 0.32, 95% CI 0.10-0.97; p = 0.044) compared with 1.0 mg/kg. Neuropathy was associated with improved PFS (HR 0.32, 95% CI 0.14-0.73; p = 0.007) and OS (HR 0.24, 95% CI 0.07-0.87; p = 0.029), while rash was associated with improved OS (HR 0.31, 95% CI 0.11-0.91; p = 0.032).
EVP was associated with frequent treatment-related adverse events requiring dose modifications, and the development of rash and peripheral neuropathy was associated with favorable survival outcomes.
Authors
Sayed Sayed, Kumar Kumar, Zarba Zarba, Mahsin Mahsin, Taleb Taleb, Alshammari Alshammari, Mairs Mairs, Basappa Basappa, Kolinsky Kolinsky, Mahoney Mahoney, Navani Navani, Cheng Cheng, Karim Karim, Lee-Ying Lee-Ying, Yip Yip, Heng Heng, North North, Alimohamed Alimohamed
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