{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:25:10Z","timestamp":1787009110572,"version":"build-2736575974"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evidence regarding treatment outcomes of third-line systemic therapy after failure of immune checkpoint inhibitor (ICI) combinations and subsequent VEGFR-TKIs in advanced renal cell carcinoma (RCC) remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively evaluated clinical data from 35 patients with advanced RCC who received third-line therapy following ICI-based first-line regimens and subsequent VEGFR-TKIs. Treatment effectiveness and safety during third-line therapy were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The most frequently administered first-line, second-line, and third-line drugs were nivolumab plus ipilimumab (n\u00a0=\u00a025, 71%), axitinib (n\u00a0=\u00a021, 60%), and cabozantinib (n\u00a0=\u00a015, 43%), respectively. Clear-cell histology was observed in 23 patients (66%), and 14 patients (40%) were classified as International Metastatic RCC Database Consortium poor risk. Median progression-free survival (PFS) and overall survival (OS) from third-line therapy initiation were 7.43 and 15.2\u00a0months, respectively, with an objective response rate of 11%. Clear-cell histology (hazard ratio [HR] 0.30, p\u00a0=\u00a00.0131) and Karnofsky Performance Status \u226580% (HR 0.27, P\u00a0=\u00a0.0157) were associated with longer OS after multivariable adjustment. Grade\u00a0\u2265\u00a03 adverse events occurred in 13 patients (37%). Dose reduction, treatment interruption, and treatment discontinuation were required in 14 (40%), 14 (40%), and 5 (14%) patients, respectively. In the subgroup receiving the most common treatment sequence\u2014first-line nivolumab plus ipilimumab followed by VEGFR-TKIs (n\u00a0=\u00a025)\u2014median PFS and OS were 10.3 and 17.3\u00a0months, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Third-line systemic therapy following ICI combinations and sequential VEGFR-TKIs shows feasible clinical effectiveness and manageable toxicity in real-world patients with advanced RCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jjco\/hyag037","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:27:32Z","timestamp":1771331252000},"page":"757-764","source":"Crossref","is-referenced-by-count":1,"title":["Real-world outcomes of third-line systemic therapy after immune checkpoint inhibitor combinations and subsequent VEGFR-TKIs in advanced renal cell carcinoma"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5146-656X","authenticated-orcid":false,"given":"Hiroki","family":"Ishihara","sequence":"first","affiliation":[{"name":"Department of Urology, Saiseikai Kawaguchi General Hospital , 5-11-5 Nishikawaguchi, Kawaguchi, Saitama, 332-8558 ,","place":["Japan"]},{"name":"Department of Urology, Tokyo Women\u2019s Medical University , 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Urology, Tokyo Women\u2019s Medical University Adachi Medical Center , 4-33-1 Kouhoku, Adachi-ku, Tokyo, 123-8558 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Nemoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Jyoban Hospital , Uenodai 57, Joban Kamiyunagayamachi, Iwaki Fukushima, 972-8322 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Department of Urology, Saiseikai Kazo Hospital , 1680 Kamitakayanagi, Kazo, Saitama, 347-0101 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Urology, Tokyo Women\u2019s Medical University , 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Urology, Tokyo Women\u2019s Medical University , 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Shimmura","sequence":"additional","affiliation":[{"name":"Department of Urology, Jyoban Hospital , Uenodai 57, Joban Kamiyunagayamachi, Iwaki Fukushima, 972-8322 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunobu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Saiseikai Kawaguchi General Hospital , 5-11-5 Nishikawaguchi, Kawaguchi, Saitama, 332-8558 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3834-0153","authenticated-orcid":false,"given":"Kazuhiko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Urology, Tokyo Women\u2019s Medical University , 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpei","family":"Iizuka","sequence":"additional","affiliation":[{"name":"Department of Urology, Tokyo Women\u2019s Medical University , 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 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