{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:51:23Z","timestamp":1791571883151,"version":"4.3.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Enfortumab vedotin (EV), pembrolizumab, and EV plus pembrolizumab (EV\/P) have rapidly reshaped the treatment landscape of advanced urothelial carcinoma, but toxicity increasingly determines treatment delivery, treatment continuity, and real-world benefit. As EV\/P moves into broader clinical use, clinicians must distinguish adverse events related to antibody-drug conjugate exposure from immune-mediated toxicities and recognize syndromes in which both mechanisms may contribute. In this practical, mechanism-informed review, we synthesize pivotal trials, mature follow-up reports, and representative real-world cohorts describing the safety of EV monotherapy, pembrolizumab monotherapy, and EV\/P in urothelial carcinoma. Because adverse-event reporting and ascertainment are heterogeneous across studies, including differences in preferred terms, composite categories, grading frameworks, and treatment-related versus all-cause reporting, we emphasize clinically interpretable patterns rather than pooled estimates. Enfortumab vedotin monotherapy is characterized by cutaneous toxicity, peripheral neuropathy, hyperglycemia, dysgeusia, and ocular events, including early epithelial\/metabolic events and cumulative neuropathy. Pembrolizumab monotherapy has a lower overall high-grade toxicity burden but is defined by immune-mediated endocrinopathies, pneumonitis, hepatitis, colitis, and nephritis. Combination therapy produces a predictable overlap of these toxicity domains, creating diagnostic and management challenges for syndromes such as skin toxicity, diarrhea, fatigue, and pulmonary symptoms. We provide comparative visual toxicity signatures, regimen-specific summary tables, temporal toxicity mapping, and a pragmatic attribution framework that classifies events as EV-predominant, immune-predominant, overlap\/indeterminate, or high-risk requiring initial interruption of both agents. This review aims to support bedside recognition, provisional attribution, early management, and safer implementation of EV\/P in contemporary urothelial carcinoma practice.<\/jats:p>","DOI":"10.1093\/oncolo\/oyag371","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:27:37Z","timestamp":1789756057000},"source":"Crossref","is-referenced-by-count":0,"title":["Toxicity attribution during enfortumab vedotin plus pembrolizumab therapy in urothelial carcinoma: a practical framework"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8668-6741","authenticated-orcid":false,"given":"Jabra","family":"Zarka","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7643-2836","authenticated-orcid":false,"given":"Daniel S","family":"Childs","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7268-5077","authenticated-orcid":false,"given":"Miguel","family":"Muniz Rincon","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0086-0556","authenticated-orcid":false,"given":"Ali","family":"Tarhini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0461-6174","authenticated-orcid":false,"given":"Albert","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-2619","authenticated-orcid":false,"given":"Lisa A","family":"Kottschade","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetomir N","family":"Markovic","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United 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A","family":"Costello","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-0239","authenticated-orcid":false,"given":"Jacob J","family":"Orme","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2026100914064330100_oyag371-B1","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 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