{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:58:16Z","timestamp":1792706296411,"version":"4.5.0"},"reference-count":17,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023368","name":"Eisai Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023368","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007052","name":"Memorial Sloan-Kettering Cancer Center","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100007052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment\u2010na\u00efve adults with aRCC were randomized to: lenvatinib (20\u2009mg PO QD in 21\u2010day cycles) plus pembrolizumab (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009355; 200\u2009mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009357; 50\u2009mg PO QD; 4 weeks on\/2 weeks off). The most common (lenvatinib plus pembrolizumab; sunitinib, respectively) metastatic site was lung (71.0%; 63.9%), followed by lymph node (45.6%; 43.7%), bone (22.5%; 24.9%), and liver (17.7%; 19.6%). Across treatment arms, \u226565% had two or more metastatic organs\/sites involved, &gt;80% of patients had nontarget lesions, and ~45% had baseline sums of diameters of target lesions \u226560\u2009mm. Lenvatinib plus pembrolizumab demonstrated greater progression\u2010free survival, objective response rate, and duration of response versus sunitinib across evaluable subgroups regardless of site or size of baseline metastasis or number of metastatic sites at baseline. Overall survival generally trended to favor lenvatinib plus pembrolizumab versus sunitinib; and tumor shrinkage was greater across sites (lung, lymph node, liver, and bone) for patients in the lenvatinib\u2010plus\u2010pembrolizumab arm versus the sunitinib arm. These results further support lenvatinib plus pembrolizumab as a standard\u2010of\u2010care in patients with aRCC regardless of site or size of baseline metastasis or the number of metastatic sites.\n                  <\/jats:p>","DOI":"10.1002\/ijc.35288","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T05:50:10Z","timestamp":1735537810000},"page":"1326-1335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the\n                    <scp>CLEAR<\/scp>\n                    trial"],"prefix":"10.1002","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2083-7687","authenticated-orcid":false,"given":"Viktor","family":"Gr\u00fcnwald","sequence":"first","affiliation":[{"name":"Interdisciplinary Genitourinary Oncology, Clinic for Urology, Clinic for Medical Oncology University Hospital Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana R.","family":"McKay","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Buchler","sequence":"additional","affiliation":[{"name":"Department of Oncology, First Faculty of Medicine Charles University and Thomayer University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Eto","sequence":"additional","affiliation":[{"name":"Department of Urology Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5084-9326","authenticated-orcid":false,"given":"Se Hoon","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Takagi","sequence":"additional","affiliation":[{"name":"Department of Urology Tokyo Women's Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Zanetta","sequence":"additional","affiliation":[{"name":"Department of Oncology Georges\u2010Fran\u00e7ois Leclerc Cancer Centre  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1087-1147","authenticated-orcid":false,"given":"Daniel","family":"Keizman","sequence":"additional","affiliation":[{"name":"Department of Oncology, Tel\u2010Aviv Sourasky Medical Center and School of Medicine Tel\u2010Aviv University  Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO) Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"N\u00e9grier","sequence":"additional","affiliation":[{"name":"University of Lyon, Centre L\u00e9on B\u00e9rard  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Lyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oncology and Internal Medicine University of Ulsan College of Medicine, Asan Medical Center  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology A, Policlinico Umberto 1 La Sapienza Universit\u00e0 di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Bedke","sequence":"additional","affiliation":[{"name":"Department of Urology and Transplantation Surgery Eva Mayr\u2010Stihl Cancer Center, Klinikum Stuttgart  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4574-6522","authenticated-orcid":false,"given":"Michael","family":"Staehler","sequence":"additional","affiliation":[{"name":"Department of Urology University Hospital of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kollmannsberger","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology BC Cancer \u2013 Vancouver Cancer Centre  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni K.","family":"Choueiri","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Motzer","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Burgents","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Xie","sequence":"additional","affiliation":[{"name":"Biostatistics, Eisai Inc.  Nutley New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinyere E.","family":"Okpara","sequence":"additional","affiliation":[{"name":"Clinical Research, Eisai Ltd.  Hatfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Powles","sequence":"additional","affiliation":[{"name":"Department of Oncology The Royal Free NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.21869"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-97365-6"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44226-y"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2019.10.002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035716"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2022.100640"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20822-2"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1223282"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01569"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajur.2016.08.006"},{"issue":"661","key":"e_1_2_11_12_1","first-page":"e7","article-title":"Metastatic renal cell carcinoma: patterns and predictors of metastases\u2014a contemporary population\u2010based series","volume":"35","author":"Chandrasekar T","year":"2017","journal-title":"Urol Oncol"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq554"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712126"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00290-X"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.6_suppl.687"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1816714"},{"key":"e_1_2_11_18_1","unstructured":"MotzerRJ PowlesT HutsonT et al.Characterization of tumor response with lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma: final overall survival analysis of the CLEAR study (4\u2010year median follow up). Poster presented at: Kidney Cancer Research Summit (KCRS); July 13\u201314 2023; Boston MA USA."}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.35288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T23:34:50Z","timestamp":1739144090000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.35288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,30]]},"references-count":17,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/ijc.35288"],"URL":"https:\/\/doi.org\/10.1002\/ijc.35288","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,30]]},"assertion":[{"value":"2024-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}