{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:55:34Z","timestamp":1791262534742,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Cancer Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To compare differences in clinical outcomes between dual immune checkpoint blockade and immunotherapy plus tyrosine kinase inhibitors (TKIs) as first\u2010line treatment for metastatic renal cell carcinoma in routine clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Retrospective multicenter cohort study including 311 patients with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate or poor\u2010risk metastatic RCC who received first\u2010line immune checkpoint inhibitor (ICI)\u2010based combination therapy between 2018 and 2023. Patients were treated with either ICI\u2009+\u2009ICI or ICI\u2009+\u2009TKI. Inverse probability of treatment weighting (IPTW) was applied to reduce baseline imbalances. Progression\u2010free survival (PFS), second progression\u2010free survival (PFS2), overall survival (OS), objective response rate (ORR), and duration of response (DOR) were analyzed using weighted survival models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After adjustment, ICI\u2009+\u2009TKI was associated with a trend toward longer PFS compared with ICI\u2009+\u2009ICI (median 28.7 vs. 16.6\u2009months, HR 0.69,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.050). No significant differences were observed in PFS2 (median 46.6 vs. 35.5\u2009months, HR 0.84,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.436) or OS (median 57.4 vs. 57.0\u2009months, HR 1.01,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.965). ORR (56.5% vs. 52.2%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.473) and DOR (median 54.6 vs. 44.9\u2009months, HR 0.83,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.502) were comparable. Subgroup analysis suggested more noticeable PFS benefit with ICI\u2009+\u2009TKI in intermediate\u2010risk patients and those without central nervous system or bone metastases, whereas OS was similar across all subgroups. The incidence of grade \u2265\u20093 adverse events was comparable between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this real\u2010world cohort, TKI\u2010containing combinations were associated with improved initial disease control, whereas no statistically significant difference in long\u2010term survival was observed between treatment strategies. Given the retrospective design and potential for residual confounding despite IPTW adjustment, these findings should be interpreted with caution. Treatment selection should therefore be individualized according to therapeutic priorities, such as the need for initial tumor control versus the expectation of sustained immune\u2010mediated benefit.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72265","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:27:12Z","timestamp":1789536432000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real\u2010World Comparison of Dual Checkpoint Blockade and Immunotherapy Plus\n                    <scp>TKIs<\/scp>\n                    in Metastatic\n                    <scp>RCC<\/scp>"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2841-1998","authenticated-orcid":false,"given":"Kojiro","family":"Ohba","sequence":"first","affiliation":[{"name":"Department of Urology and Renal Transplantation Nagasaki University Hospital  Nagasaki 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Hokkaido University Hospital  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8290-0322","authenticated-orcid":false,"given":"Toru","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Urology Oita University Faculty of Medicine  Oita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-4281","authenticated-orcid":false,"given":"Toshitaka","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Urology Oita University Faculty of Medicine  Oita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Sekine","sequence":"additional","affiliation":[{"name":"Department of Urology Akita University Graduate School of Medicine  Akita 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