{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:10:50Z","timestamp":1789056650838,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Limited data are available on the midterm outcomes of combination therapy with immune checkpoint inhibitors and VEGFR\u2010TKIs (IO\u2010TKI) for advanced renal cell carcinoma (RCC) in real\u2010world settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively evaluated data from 68 patients who received lenvatinib plus pembrolizumab (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914), cabozantinib plus nivolumab (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920), pembrolizumab plus axitinib (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200923), or avelumab plus axitinib (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911) as first\u2010line therapy for advanced RCC. All patients initiated IO\u2010TKI at least 3\u2009years before the data\u2010cutoff, ensuring a potentially minimum follow\u2010up of 3\u2009years. Effectiveness and safety profiles were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During a median follow\u2010up of 32.7\u2009months, the median progression\u2010free survival (PFS) and overall survival (OS) were 19.9 and 46.7\u2009months, respectively. The objective response rate was 57%. In subgroup analysis, histology was associated with survival outcomes; median PFS (23.0 vs. 13.8\u2009months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0503) and OS (not reached vs. 37.4\u2009months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0016) were longer in patients with clear\u2010cell RCC than in those with non\u2010clear\u2010cell RCC. Regarding safety, Grade 3 adverse events occurred in 44 patients (65%). Treatment discontinuation of both drugs was required in 14 patients (21%), and discontinuation of one drug in 21 patients (31%). High\u2010dose glucocorticoids (\u2265\u200940\u2009mg prednisone\/day) were required in 10 patients (15%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>With a minimum of 3\u2009years of follow\u2010up, IO\u2010TKI demonstrated feasible effectiveness and manageable safety in patients with advanced RCC in the real world. More effective treatment strategies and novel therapeutic targets are needed for patients with non\u2010clear\u2010cell RCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iju.70444","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:35:32Z","timestamp":1774442132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Midterm Outcomes of Combination Therapy With Immune Checkpoint Inhibitors and\n                    <scp>VEGFR<\/scp>\n                    \u2010\n                    <scp>TKIs<\/scp>\n                    in Real\u2010World Patients With Advanced Renal Cell Carcinoma"],"prefix":"10.1111","volume":"33","author":[{"given":"Hiroki","family":"Ishihara","sequence":"first","affiliation":[{"name":"Department of Urology Saiseikai Kawaguchi General Hospital  Saitama Japan"},{"name":"Department of Urology Tokyo Women's Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanaka","family":"Katsurayama","sequence":"additional","affiliation":[{"name":"Department of Urology Tokyo Women's Medical University Adachi Medical Center  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Nemoto","sequence":"additional","affiliation":[{"name":"Department of Urology Jyoban Hospital  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Department of Urology Saiseikai Kazo Hospital  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Urology Tokyo Women's Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Urology Tokyo Women's Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Shimmura","sequence":"additional","affiliation":[{"name":"Department of Urology Jyoban Hospital  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunobu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Urology Saiseikai Kawaguchi General Hospital  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Urology Tokyo Women's Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpei","family":"Iizuka","sequence":"additional","affiliation":[{"name":"Department of Urology Tokyo Women's Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunenori","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Urology Tokyo Women's Medical University Adachi Medical Center  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-0943","authenticated-orcid":false,"given":"Toshio","family":"Takagi","sequence":"additional","affiliation":[{"name":"Department of Urology Tokyo Women's Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035716"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026982"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1816714"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2024.03.015"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.102994"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.06.006"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.12.008"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-025-04019-x"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-024-02633-w"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1605282"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.15230"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2024.102225"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-024-02618-9"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.15345"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.04.004"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01569"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.09.006"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_12_20_1","unstructured":"National Cancer Institute \u201cNational Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.4 \u201d(2024) http:\/\/evs.nci.nih.gov\/ftp1\/CTCAE\/About.html."},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-024-02471-w"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2025.06.019"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2013.06.035"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2017.01.016"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-019-00660-6"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyae001"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2025.1891"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-025-01056-0"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.70091"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30436-8"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.16148"}],"container-title":["International Journal of Urology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iju.70444","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/iju.70444","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iju.70444","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:59:36Z","timestamp":1787669976000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iju.70444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/iju.70444"],"URL":"https:\/\/doi.org\/10.1111\/iju.70444","archive":["Portico"],"relation":{},"ISSN":["0919-8172","1442-2042"],"issn-type":[{"value":"0919-8172","type":"print"},{"value":"1442-2042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70444"}}