{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T01:47:22Z","timestamp":1782956842215,"version":"3.54.5"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Nivolumab plus ipilimumab has demonstrated improved survival for treatment-na\u00efve advanced clear cell renal cell carcinoma (RCC). A series of clinical trials evaluated the effect of salvage nivolumab plus ipilimumab in patients without an objective response to nivolumab. Given the size and heterogeneity of these studies, we performed a pooled analysis to better inform the activity of nivolumab plus ipilimumab after nivolumab.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and Methods<\/jats:title>\n                  <jats:p>Eligible patients included those with advanced clear cell RCC having received no prior immunotherapy. The primary objective was confirmed objective response rate (ORR) by investigator-assessment. Secondary objectives included progression-free survival (PFS) and overall survival (OS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The analysis included 410 patients with clear cell RCC, of whom 340 (82.9%) had IMDC intermediate\/poor risk disease, and 137 (33.4%) had prior treatment. The 16-18-week ORR to nivolumab prior to nivolumab plus ipilimumab was 22.7% (n = 93), and best ORR to nivolumab was 25.1% (n = 103). Two hundred and thirty (56.1%) patients treated with nivolumab received nivolumab plus ipilimumab at a median of 16 weeks (IQR 9-19) after initiation of nivolumab [27.0% (n = 62) with stable disease and 73.0% (n = 168) with progressive disease to nivolumab]. The ORR to nivolumab plus ipilimumab was 12.6% (n = 29). Six-month PFS on nivolumab plus ipilimumab was 37% (95% CI, 27-47). Median follow-up was 34.3 months and 3-year OS was 59% (95% CI, 53-64) from nivolumab start.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>A small subset of patients lacking a response to nivolumab derive benefit from salvage nivolumab plus ipilimumab. When possible, both drugs should be given in concomitantly, rather in an adaptive fashion.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyad298","type":"journal-article","created":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T19:23:10Z","timestamp":1699730590000},"page":"324-331","source":"Crossref","is-referenced-by-count":4,"title":["A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab\/Ipilimumab After Nivolumab in Renal Cell Carcinoma"],"prefix":"10.1093","volume":"29","author":[{"given":"Rana R","family":"McKay","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA , USA"},{"name":"Department of Urology, University of California San Diego , La Jolla, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Leucht","sequence":"additional","affiliation":[{"name":"Department of Urology, Universitaetsklinikum Jena , Jena , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-8000","authenticated-orcid":false,"given":"Wanling","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana-Farber Cancer Institute , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opeyemi","family":"Jegede","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana-Farber Cancer Institute , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale University , New Haven, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-9924","authenticated-orcid":false,"given":"Michael B","family":"Atkins","sequence":"additional","affiliation":[{"name":"Department of Medicine, Georgetown University , Washington, DC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Oliver","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Urology, Universitaetsklinikum Jena , Jena , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9201-3217","authenticated-orcid":false,"given":"Toni K","family":"Choueiri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dana-Farber Cancer Institute , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"key":"2024041017265494300_CIT0001","first-page":"1803","article-title":"Nivolumab versus everolimus in advanced renal-cell carcinoma","volume-title":"N Engl J Med","author":"Motzer","year":"2015"},{"key":"2024041017265494300_CIT0002","first-page":"994","article-title":"Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: a randomised, open-label, phase 3 trial","volume-title":"Lancet Oncol","author":"Cella","year":"2016"},{"key":"2024041017265494300_CIT0003","first-page":"4156","article-title":"Nivolumab versus everolimus in patients with advanced renal cell carcinoma: updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial","volume-title":"Cancer","author":"Motzer","year":"2020"},{"key":"2024041017265494300_CIT0004","first-page":"1277","article-title":"Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma","volume-title":"N Engl J Med","author":"Motzer","year":"2018"},{"key":"2024041017265494300_CIT0005","first-page":"297","article-title":"Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial","volume-title":"Lancet 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nivolumab\/ipilimumab in treatment-naive patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B)","volume-title":"J ImmunoTher Cancer","author":"Atkins","year":"2023"},{"issue":"7","key":"2024041017265494300_CIT0010","doi-asserted-by":"crossref","first-page":"S1206","DOI":"10.1016\/j.annonc.2022.07.1553","article-title":"Efficacy of a tailored approach with nivolumab and nivolumab\/ipilimumab as immunotherapeutic boost in metastatic renal cell carcinoma: final results of TITAN-RCC","volume":"33","author":"Grimm","year":"2022","journal-title":"Ann Oncol"},{"key":"2024041017265494300_CIT0011","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1093\/annonc\/mdz394.051","article-title":"Tailored immunotherapy approach with nivolumab in advanced renal cell carcinoma (TITAN-RCC)","volume":"30","author":"Grimm","year":"2019","journal-title":"Ann Oncol"},{"key":"2024041017265494300_CIT0012","first-page":"1020","article-title":"Open-label, single-arm phase ii study of pembrolizumab monotherapy as first-line therapy in patients with advanced clear cell renal cell carcinoma","volume-title":"J Clin Oncol","author":"McDermott","year":"2021"},{"key":"2024041017265494300_CIT0013","first-page":"e005780","article-title":"FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy","volume-title":"J ImmunoTher Cancer","author":"Choueiri","year":"2022"},{"key":"2024041017265494300_CIT0014","first-page":"946","article-title":"Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (study 111\/KEYNOTE-146): a phase 1b\/2 study","volume-title":"Lancet Oncol","author":"Lee","year":"2021"},{"key":"2024041017265494300_CIT0015","first-page":"185","article-title":"Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial","volume-title":"Lancet","author":"Pal","year":"2023"},{"key":"2024041017265494300_CIT0016","first-page":"909","article-title":"Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma","volume-title":"Nat Med","author":"Braun","year":"2020"},{"key":"2024041017265494300_CIT0017","first-page":"632","article-title":"Progressive immune dysfunction with advancing disease stage in renal cell carcinoma","volume-title":"Cancer Cell","author":"Braun","year":"2021"}],"container-title":["The 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