{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:50:20Z","timestamp":1790887820502,"version":"4.1.0"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"Importance<\/jats:title>Studies with nivolumab, an approved therapy for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy, demonstrate improved outcomes with added high-dose ipilimumab.<\/jats:p><\/jats:sec>Objective<\/jats:title>To assess efficacy and safety of a tailored approach using nivolumab\u2009+\u2009ipilimumab as an immunotherapeutic boost for mUC.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>In this phase 2 nonrandomized trial, patients with mUC composed 2 cohorts. Cohort 1 received first-line or second-\/third-line nivolumab with escalating doses of ipilimumab, and cohort 2 received second-\/third-line nivolumab with high-dose ipilimumab. Recruitment spanned 26 sites in Germany and Austria from August 8, 2017, to February 18, 2021. All patients had a 70% or higher Karnofsky Performance Score and measurable disease per Response Evaluation Criteria in Solid Tumours, version 1.1.<\/jats:p><\/jats:sec>Interventions<\/jats:title>All patients initiated 4 doses of 240-mg nivolumab (1\u00d7 every 2 wk). Week 8 nonresponders received nivolumab\u2009+\u2009ipilimumab (1\u00d7 every 3 wk). Cohort 1 received 2 doses of 3-mg\/kg nivolumab\u2009+\u20091-mg\/kg ipilimumab followed by 2 doses of 1-mg\/kg nivolumab\u2009+\u20093-mg\/kg ipilimumab if no response. Due to safety concerns, cohort 1 treatment was halted, and first-line cohort 2 treatment was not pursued. Cohort 2 received 2 to 4 doses of 1-mg\/kg nivolumab\u2009+\u20093-mg\/kg ipilimumab. Responders continued with nivolumab maintenance but could receive nivolumab\u2009+\u2009ipilimumab for later progression.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary end point was objective response rate.<\/jats:p><\/jats:sec>Results<\/jats:title>The study comprised 169 patients (118 [69.8%] men; median [range] age, 68 [37-84] years): 86 in cohort 1 (42 first-line; 44 second-\/third-line) and 83 in cohort 2. The median (IQR) follow-up times were 10.4 (4.2-23.5) months (first-line cohort 1), 7.5 (3.1-23.8) months (second-\/third-line cohort 1), and 6.2 (3.2-22.7) months (cohort 2). Response rates to nivolumab induction were 12\/42 (29%, first-line cohort 1), 10\/44 (23%, second-\/third-line cohort 1), and 17\/83 (20%, cohort 2). Response rates to a tailored approach were 20\/42 (48% [90% CI, 34%-61%], first-line cohort 1), 12\/44 (27% [90% CI, 17%-40%], second-\/third-line cohort 1), and 27\/83 (33% [90% CI, 23%-42%], cohort 2). Three-year overall survival rates for first-line cohort 1, second-\/third-line cohort 1, and cohort 2 using the Kaplan-Meier method were 32% (95% CI, 17%-49%), 19% (95% CI, 8%-33%), and 34% (95% CI, 23%-44%), respectively.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this nonrandomized trial, although first-line cohort 1 treatment improved objective response rates, considerable progression events urge caution with this as a first-line therapy. Second-\/third-line cohort 1 treatment did not improve response rates compared with nivolumab monotherapy. However, added high-dose ipilimumab may improve tumor response and survival in patients with mUC.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT03219775<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2024.0938","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T15:00:52Z","timestamp":1715266852000},"page":"755","source":"Crossref","is-referenced-by-count":7,"title":["Nivolumab\u2009+\u2009Ipilimumab as Immunotherapeutic Boost in Metastatic Urothelial Carcinoma"],"prefix":"10.1001","volume":"10","author":[{"given":"Marc-Oliver","family":"Grimm","sequence":"first","affiliation":[{"name":"Department of Urology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schostak","sequence":"additional","affiliation":[{"name":"Department of Urology, Magdeburg University Hospital, Magdeburg, 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