{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:09:30Z","timestamp":1788944970644,"version":"build-2803163510"},"reference-count":14,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>Background: 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. Methods: We conducted a retrospective, multicenter analysis of 60 la\/mUC patients treated with first-line EVP in Alberta, Canada (September 2024\u2013January 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. Results: 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\u20130.68; p = 0.004) and OS (HR 0.32, 95% CI 0.10\u20130.97; p = 0.044) compared with 1.0 mg\/kg. Neuropathy was associated with improved PFS (HR 0.32, 95% CI 0.14\u20130.73; p = 0.007) and OS (HR 0.24, 95% CI 0.07\u20130.87; p = 0.029), while rash was associated with improved OS (HR 0.31, 95% CI 0.11\u20130.91; p = 0.032). Conclusions: 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.<\/jats:p>","DOI":"10.3390\/curroncol33090542","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:05:43Z","timestamp":1788941143000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicity, Dose Intensity, and Clinical Outcomes with First-Line Enfortumab Vedotin Plus Pembrolizumab in Advanced Urothelial Carcinoma: A Multicenter Real-World Study"],"prefix":"10.3390","volume":"33","author":[{"given":"Samad","family":"Sayed","sequence":"first","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishikesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Cross Cancer Institute, University of Alberta, Edmonton, AB T6G1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3642-4035","authenticated-orcid":false,"given":"Martin","family":"Zarba","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md","family":"Mahsin","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"Taleb","sequence":"additional","affiliation":[{"name":"Jack Ady Cancer Centre, Alberta Health Services, Lethbridge, AB T1J1W5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4565-6092","authenticated-orcid":false,"given":"Lateefah","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Mairs","sequence":"additional","affiliation":[{"name":"Alberta Health Services, Red Deer, AB T4N4E7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3163-9902","authenticated-orcid":false,"given":"Naveen","family":"Basappa","sequence":"additional","affiliation":[{"name":"Cross Cancer Institute, University of Alberta, Edmonton, AB T6G1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kolinsky","sequence":"additional","affiliation":[{"name":"Cross Cancer Institute, University of Alberta, Edmonton, AB T6G1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Mahoney","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6795-009X","authenticated-orcid":false,"given":"Vishal","family":"Navani","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Cheng","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safiya","family":"Karim","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0913-6046","authenticated-orcid":false,"given":"Richard","family":"Lee-Ying","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Yip","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Y. C.","family":"Heng","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"North","sequence":"additional","affiliation":[{"name":"Cross Cancer Institute, University of Alberta, Edmonton, AB T6G1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimira","family":"Alimohamed","sequence":"additional","affiliation":[{"name":"Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB T2N5G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","first-page":"e70090","article-title":"Global Cancer Statistics 2024: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 34 Cancers in 186 Countries","volume":"76","author":"Sung","year":"2026","journal-title":"CA. Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.1200\/JCO.2005.07.757","article-title":"Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, with Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients with Bladder Cancer","volume":"23","author":"Sengelov","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ejca.2005.08.032","article-title":"Seven Year Update of an EORTC Phase III Trial of High-Dose Intensity M-VAC Chemotherapy and G-CSF versus Classic M-VAC in Advanced Urothelial Tract Tumours","volume":"42","author":"Sternberg","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1200\/JCO.23.01983","article-title":"NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer","volume":"42","author":"Tran","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1756287219839285","DOI":"10.1177\/1756287219839285","article-title":"Pembrolizumab in the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma: Clinical Trial Evidence and Experience","volume":"11","author":"Crist","year":"2019","journal-title":"Ther. Adv. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Patel, D.M., Mateen, R., Qaddour, N., Carrillo, A., Verschraegen, C., Yang, Y., Li, Z., Sundi, D., Mortazavi, A., and Collier, K.A. (2024). A Comprehensive Review of Immunotherapy Clinical Trials for Metastatic Urothelial Carcinoma: Immune Checkpoint Inhibitors Alone or in Combination, Novel Antibodies, Cellular Therapies, and Vaccines. Cancers, 16.","DOI":"10.3390\/cancers16020335"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1056\/NEJMoa2312117","article-title":"Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer","volume":"390","author":"Powles","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1001\/jamadermatol.2021.5476","article-title":"Association of Cutaneous Immune-Related Adverse Events with Increased Survival in Patients Treated with Anti\u2013Programmed Cell Death 1 and Anti\u2013Programmed Cell Death Ligand 1 Therapy","volume":"158","author":"Tang","year":"2022","journal-title":"JAMA Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10147-024-02672-3","article-title":"Treatment-Related Skin Reactions in Enfortumab Vedotin as a Surrogate Marker of Survival and Treatment Response","volume":"30","author":"Nagayama","year":"2025","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.annonc.2025.05.536","article-title":"Enfortumab Vedotin plus Pembrolizumab in Untreated Locally Advanced or Metastatic Urothelial Carcinoma: 2.5-Year Median Follow-Up of the Phase III EV-302\/KEYNOTE-A39 Trial","volume":"36","author":"Powles","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102453","DOI":"10.1016\/j.clgc.2025.102453","article-title":"Real-World Outcomes of Enfortumab Vedotin and Pembrolizumab in Advanced Urothelial Carcinoma: A Multicenter Retrospective Analysis","volume":"23","author":"Jain","year":"2025","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vlachou, E., Johnson, B.A., McConkey, D., Jing, Y., Matoso, A., Hahn, N.M., and Hoffman-Censits, J. (2024). Enfortumab Vedotin\u2013Related Cutaneous Toxicity Correlates with Overall Survival in Patients with Urothelial Cancer: A Retrospective Experience. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1377842"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e223","DOI":"10.1093\/oncolo\/oyac001","article-title":"Management of Dermatologic Events Associated With the Nectin-4-Directed Antibody-Drug Conjugate Enfortumab Vedotin","volume":"27","author":"Lacouture","year":"2022","journal-title":"Oncologist"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1158\/2767-9764.CRC-25-0039","article-title":"Novel Pretreatment Autoantibodies Correlate with Enfortumab Vedotin\u2013Related Dermatologic Events in Patients with Advanced Urothelial Cancer","volume":"5","author":"Vlachou","year":"2025","journal-title":"Cancer Res. Commun."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/9\/542\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:51:05Z","timestamp":1788943865000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/9\/542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":14,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["curroncol33090542"],"URL":"https:\/\/doi.org\/10.3390\/curroncol33090542","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}