{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:36:55Z","timestamp":1777718215864,"version":"3.51.4"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Antibody-drug conjugates (ADCs) are revolutionizing the treatment landscape of advanced urothelial carcinoma (aUC). We systematically reviewed the PubMed and Embase databases for published clinical trials evaluating ADC-combination regimens in aUC. We extracted safety and efficacy outcomes, including objective-response rate (ORR), adverse events (AEs), and \u2265 grade 3 AEs. We excluded narrative reviews, retrospective studies, and case reports. Two independent reviewers screened titles and abstracts for relevance, followed by a full-text review for eligibility. A total of 645 patients from 5 trials investigating anti-nectin-4 (enfortumab vedotin, EV), anti-TROP2 (sacituzumab govitecan, SG), and anti-HER2 (disitamab vedotin, DV) ADCs were identified. We recorded a pooled ORR of 65%. We recorded a pooled risk rate for all-grade toxicity of 57%. The most prevalent any-grade AEs were peripheral sensory neuropathy 52% (95% CI, 45%-59%), fatigue 45% (95% CI, 28%-64%), and diarrhea 42% (95% CI, 16%-74%). Peripheral sensory neuropathy, fatigue, and alopecia were more commonly observed in anti-nectin-4 regimens. Gastrointestinal (diarrhea and nausea) and hematologic (anemia and neutropenia) toxicities were more commonly observed in anti-TROP2 regimens. Hepatotoxicity was predominantly found in anti-HER2 regimens. While ADC-based combination regimens show promising responses, they also have high rates of AEs in patients with aUC.<\/jats:p>","DOI":"10.3389\/fonc.2025.1669526","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T04:13:58Z","timestamp":1759810438000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of antibody-drug conjugate combination therapy in advanced urothelial 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