{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:18:30Z","timestamp":1787764710327,"version":"build-2784847793"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100022752","name":"MSD Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022752","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":[[2026,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The combination of two immune checkpoint inhibitors (CPI) or a CPI with a tyrosine kinase inhibitor (TKI) has expanded the therapeutic options for advanced\/metastatic renal cell carcinoma (aRCC) beyond TKI monotherapy. In the absence of head\u2010to\u2010head randomized trials comparing these strategies, we estimate their real\u2010world effectiveness by emulating a hypothetical randomized trial. A total of 936 patients with aRCC from the prospective, observational, multicenter clinical registry CARAT (NCT03374267) starting first\u2010line treatment after January 15, 2019, were included. Inverse probability of treatment weighting (IPTW) was used to compare first\u2010line CPI\u2009+\u2009TKI (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009447), CPI\u2009+\u2009CPI (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009257), and TKI monotherapy (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009166). Real\u2010world progression\u2010free survival (rwPFS), overall survival (OS), and time\u2010to\u2010deterioration (TTD) of health\u2010related quality of life (HRQoL) were analyzed, also stratified by patients' prognostic risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. IPTW\u2010adjusted median rwPFS and OS independent of IMDC risk were 12.3 [10.4\u201315.6] and 29.0\u2009months [25.6\u201336.3] for TKI\u2009+\u2009CPI, 8.3 [6.5\u201310.9] and 21.9\u2009months [16.3\u201334.5] for CPI\u2009+\u2009CPI, and 8.5 [6.4\u201310.0] and 31.7\u2009months [21.0\u201340.0] for TKI monotherapy. Compared to CPI\u2009+\u2009TKI, survival tended to be worse for CPI\u2009+\u2009CPI (rwPFS: hazard ratio (HR) 1.25 [1.00\u20131.58]; OS: HR 1.25 [0.95, 1.63]). This finding was more pronounced for rwPFS in patients at intermediate risk. Median TTD of HRQoL did not substantially differ between the strategies. Despite the lack of statistically significant HR differences in rwPFS and OS, there was a trend toward superior survival with first\u2010line CPI\u2009+\u2009TKI compared to CPI\u2009+\u2009CPI. TKI monotherapy may remain a viable first\u2010line treatment option in selected patient populations. Further analyses, preferentially randomized clinical trials, are warranted.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70211","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:20:29Z","timestamp":1761762029000},"page":"1690-1702","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Head\u2010to\u2010head comparison of\n                    <scp>TKI<\/scp>\n                    and\n                    <scp>CPI<\/scp>\n                    first\u2010line treatment strategies in advanced renal cell carcinoma\u2014Real\u2010world data from the German research platform\n                    <scp>CARAT<\/scp>"],"prefix":"10.1002","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0176-4478","authenticated-orcid":false,"given":"Peter J.","family":"Goebell","sequence":"first","affiliation":[{"name":"Department of Urology University Hospital Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"B\u00f6gemann","sequence":"additional","affiliation":[{"name":"Department of Urology University Hospital Muenster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnd","family":"Nusch","sequence":"additional","affiliation":[{"name":"Praxis f\u00fcr H\u00e4matologie und Internistische Onkologie  Ratingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Gr\u00fcnwald","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine (Tumour Research) and Department for Urology West German Cancer Center, University Hospital Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Onkologie UnterEms  Leer Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyck","family":"von der Heyde","sequence":"additional","affiliation":[{"name":"Onkologische Schwerpunktpraxis  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe M.","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III SLK Clinics Heilbronn  Heilbronn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Lennartz","sequence":"additional","affiliation":[{"name":"Biostatistics iOMEDICO  Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Koska","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Health Economics iOMEDICO  Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Potthoff","sequence":"additional","affiliation":[{"name":"Medical Department iOMEDICO  Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Kaiser\u2010Osterhues","sequence":"additional","affiliation":[{"name":"Medical Department iOMEDICO  Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Gr\u00fcllich","sequence":"additional","affiliation":[{"name":"Sana Klinikum Hof  Hof 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, Interdisciplinary Center of Renal Tumors Ludwig\u2010Maximilians\u2010University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"J\u00e4nicke","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Health Economics iOMEDICO  Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Marschner","sequence":"additional","affiliation":[{"name":"Department of Haematology\/Oncology and Palliative Care Klinikum Stuttgart  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CARAT Registry Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"e_1_2_14_2_1","unstructured":"LjungbergB BexA AlbigesL et al.EAU guidelines on renal cell carninoma: update 2024.2024.https:\/\/d56bochluxqnz.cloudfront.net\/documents\/pocket-guidelines\/EAU-Pocket-on-Renal-Cell-Carcinoma-2024.pdf. 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