Real-World Efficacy and Safety of Frontline Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma: A Multicenter Study and Review of the Literature

Kıkılı, Cevat; Araz, Murat; ÜRÜN, YÜKSEL; BAŞARAN, MERT; Şener, Nur; Yazar, Aziz; Ersoy, Seval; Kılıçkap, Saadettin; ERMAN, MUSTAFA; Tanrıkulu Şimşek, Eda; Alkan, Onur; Özçelik, Hakan; Bayram, Selami; Atçı, Mustafa; Özdemir, Nuriye; Damla Açıkel Yüksel, Sakine; Güney, Gizem; Bütün, Osman; Kaplan, Muhammed; Ertürk, İsmail; ALAN, ÖZKAN; Esin, Ece; Erdem, DİLEK; Atalah, Fatih; Selvi, Oğuzhan; Çelik, Sinemis; Bilgetekin, İrem; Köse, Fatih; Hendem, Engin; SEMİZ, HÜSEYİN; Ayhan, Murat; Gedik, Ezel; Şengül, Nilay; Demirel, Ahmet; Gürbüz, Mustafa; Köylü, Bahadır; Kemik, Fatih; Gündüz, Şeyda; Kanıtez, Metin; Acısu Seven, Yasemin; Coskunpınar, Muharrem; Artan, Selay; Korkmaz, Taner; Yıldız, İbrahim; Er, Özlem; Çonay, Erhan; Kalacı, ENDER; Durukan, Mert; Akdoğan, Orhun; Atacan, Hüseyin; Karabulut, Bülent; Bilici, Ahmet; Yumuk, Perran; Selçukbiricik, Fatih; Tural, Deniz

doi:10.1016/j.clgc.2026.102594

Real-World Efficacy and Safety of Frontline Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma: A Multicenter Study and Review of the Literature

Kıkılı C. İ., Araz M., ÜRÜN Y., BAŞARAN M., Şener N., Yazar A., ...Daha Fazla

Clinical Genitourinary Cancer, cilt.24, sa.5, 2026 (SCI-Expanded, Scopus)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 24 Sayı: 5
Basım Tarihi: 2026
Doi Numarası: 10.1016/j.clgc.2026.102594
Dergi Adı: Clinical Genitourinary Cancer
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO)
Anahtar Kelimeler: Objective Response Rate, Overall Survival, Progression-Free Survival, Safety Profile, Treatment Outcomes
Ankara Üniversitesi Adresli: Evet

Özet

Background Enfortumab vedotin plus pembrolizumab (EV + P) is an established standard of care for metastatic urothelial carcinoma; however, real-world data remain limited. We evaluated clinical outcomes in patients treated in the frontline metastatic setting. Patients and Methods The primary endpoint was objective response rate (ORR); secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and safety. Median follow-up and survival outcomes were estimated using reverse and standard Kaplan–Meier methods and Cox regression analyses. Result Overall, 160 patients were included, with 148 (92.5%) receiving EV + P in the 1L. The median follow-up was 14 months. In the 1L, the median PFS was 12 months (95% CI, 6.4-17.6). The CR rate was 14.9% and the PR rate was 54.1%, resulting in an ORR of 69.0%. SD and PD were observed in 16.9% and 14.1% of patients, respectively. Among patients achieving CR or PR, the median duration of response was 20 months (95% CI, 11.3-28.6). In univariate analyses for PFS, patients with upper urinary tract tumors had significantly shorter PFS compared with those with lower urinary tract tumors (5 vs. 20 months, P = .004). Patients with ECOG PS ≥ 2 had shorter PFS than those with ECOG PS ≤ 1 (3 vs. 16 months; P = .002). De novo metastatic disease was associated with worse PFS (6 vs. 23 months, P = .07). In the 1L EV + P cohort, 12- and 24-month OS rates were 73.8% and 57.7%, respectively. In the ≥ 2-line cohort (n = 12), the ORR was 66.7%, with PR in 58.4% and CR in 8.3%; SD and PD were observed in 8.3% and 25.0% of patients, respectively. Overall, 80.6% of patients experienced at ≥ 1 treatment-related adverse event (TRAEs) of any grade, and 19 patients (13.7%) developed grade 3 to 4 TRAEs. Conclusions In this real-world cohort, EV + P demonstrated meaningful clinical activity and manageable safety as frontline therapy, consistent with EV-302.