{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:22:53Z","timestamp":1783488173755,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To compare the real\u2010world effectiveness and safety of pembrolizumab plus lenvatinib with axitinib\u2010based regimens (avelumab plus axitinib or pembrolizumab plus axitinib) as first\u2010line therapy for metastatic clear cell renal cell carcinoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 107 patients treated with immuno\u2010oncology plus vascular endothelial growth factor inhibitor combinations between 2017 and 2025. Propensity score matching (1:1, 0.2 caliper) generated 42 matched pairs. Objective response rate, progression\u2010free survival, overall survival, and adverse events were assessed. Multivariable logistic regression and Cox regression analyses were performed in the overall cohort, and conditional logistic regression and stratified Cox regression analyses were applied in the matched cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the matched cohort, pembrolizumab plus lenvatinib demonstrated a significantly higher objective response rate than axitinib\u2010based regimens. The incidence of any\u2010grade and grade \u2265\u20093 adverse events was similar between regimens. However, pembrolizumab plus lenvatinib was associated with higher rates of hypertension (including grade \u2265\u20093 hypertension), fatigue, appetite loss, and rash in the full\u2010dose subgroup. Progression\u2010free and overall survival did not differ significantly. Multivariate analyses identified pembrolizumab plus lenvatinib treatment as an independent predictor of objective response, whereas survival outcomes were associated with clinical factors rather than the regimen type.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pembrolizumab plus lenvatinib achieved a superior tumor response to axitinib\u2010based regimens, whereas survival outcomes were comparable. Treatment selection should balance enhanced antitumor activity with differences in toxicity profiles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iju.70461","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:35:29Z","timestamp":1776231329000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Real\u2010World Effectiveness and Safety of Pembrolizumab\u2013Lenvatinib Versus Axitinib\u2010Based Regimens in Metastatic Clear Cell Renal Cell Carcinoma: A Multicenter Retrospective Study"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2098-3916","authenticated-orcid":false,"given":"Kohei","family":"Kobatake","sequence":"first","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima 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Onomichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsutaro","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Urology Matsuyama Red Cross Hospital  Matsuyama Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7014-6812","authenticated-orcid":false,"given":"Nobuyuki","family":"Hinata","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1524497"},{"issue":"4","key":"e_1_2_11_3_1","first-page":"1071","article-title":"Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical 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