{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T10:10:58Z","timestamp":1792750258359,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare the differential efficacy of first\u2010line immune checkpoint inhibitor (ICI)\u2010based combined therapies among patients with intermediate\u2010 and poor\u2010risk metastatic renal cell carcinoma (mRCC), as recently, the efficacy of triplet therapy comprising nivolumab plus ipilimumab plus cabozantinib has been published.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Three databases were searched in December 2022 for randomised controlled trials (RCTs) analysing oncological outcomes in patients with mRCC treated with first\u2010line ICI\u2010based combined therapies. We performed network meta\u2010analysis (NMA) to compare the outcomes, including progression\u2010free survival (PFS) and objective response rates (ORRs), in patients with intermediate\u2010 and poor\u2010risk mRCC; we also assessed treatment\u2010related adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, seven RCTs were included in the meta\u2010analyses and NMAs. Treatment ranking analysis revealed that pembrolizumab + lenvatinib (99%) had the highest likelihood of improved PFS, followed by nivolumab + cabozantinib (79%), and nivolumab + ipilimumab + cabozantinib (77%). Notably, compared to nivolumab + cabozantinib, adding ipilimumab to nivolumab + cabozantinib did not improve PFS (hazard ratio 1.02, 95% confidence interval 0.72\u20131.43). Regarding ORRs, treatment ranking analysis also revealed that pembrolizumab + lenvatinib had the highest likelihood of providing better ORRs (99.7%). The likelihoods of improved PFS and ORRs of pembrolizumab + lenvatinib were true in both International Metastatic RCC Database Consortium (IMDC) risk groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our analyses confirmed the robust efficacy of pembrolizumab + lenvatinib as first\u2010line treatment for patients with intermediate or poor IMDC risk mRCC. Triplet therapy did not result in superior efficacy. Considering both toxicity and the lack of mature overall survival data, triplet therapy should only be considered in selected patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.16336","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T23:59:46Z","timestamp":1714003186000},"page":"323-336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["First\u2010line immunotherapy of metastatic renal cell carcinoma: an updated network meta\u2010analysis including triplet therapy"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-0712","authenticated-orcid":false,"given":"Takafumi","family":"Yanagisawa","sequence":"first","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center Medical University of Vienna  Vienna Austria"},{"name":"Department of Urology The Jikei University School of Medicine  Tokyo 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