{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:44:44Z","timestamp":1785300284334,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune checkpoint inhibitor\/tyrosine kinase inhibitor (ICI\/TKI) combinations are a new standard of care for the initial treatment of metastatic renal cell carcinoma (mRCC). Their efficacy and toxicity beyond the first\u2010line setting remain poorly defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively reviewed charts for 85 adults with mRCC of any histology receiving combination of ICI\/TKI in any line of treatment at two academic centers as of 05\/01\/2020. We collected clinical, pathological, and treatment\u2010related variables. Outcomes including objective response rate (ORR), progression\u2010free survival (PFS), and toxicity were analyzed via descriptive statistics and the Kaplan\u2013Meier method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients received pembrolizumab, nivolumab, avelumab, or nivolumab\u2013ipilimumab, with concurrent use of sunitinib, axitinib, pazopanib, lenvatinib, or cabozantinib. Thirty\u2010three patients received first\u2010line ICI\/TKI therapy, while 52 received \u2265 second\u2010line ICI\/TKI. The efficacy of ICI\/TKI therapy decreased with increasing lines of treatment (ORR: 56.7%, 37.5%, 21.4%, and 21%; median PFS [mPFS]: 15.2, 14.2, 10.1, and 6.8\u00a0months, for first, second, third, and \u2265 fourth line therapy, respectively). In the \u2265 second\u2010line setting, ICI\/TKI was most useful in patients who received ICI only, with an ORR of 50% and a mPFS of 9.1\u00a0months. Efficacy was limited in patients who received both TKI and ICI previously, with an ORR of 20% and a mPFS of 5.5\u00a0months. Overall, \u2265 second\u2010line ICI\/TKI was tolerable with 25 of 52 (52%) patients developing grade\u00a0\u22653 adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ICI\/TKI combination therapy is feasible and safe beyond the first\u2010line setting. Prior treatment history appears to impact efficacy but has a lesser effect on safety\/tolerability.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4679","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T05:26:15Z","timestamp":1647667575000},"page":"3106-3114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Combining immune checkpoint inhibition plus tyrosine kinase inhibition as first and subsequent treatments for metastatic renal cell carcinoma"],"prefix":"10.1002","volume":"11","author":[{"given":"Yuanquan","family":"Yang","sequence":"first","affiliation":[{"name":"Genitourinary Oncology Section, Division of Medical Oncology The Ohio State University Comprehensive Cancer Center \u2013 James Cancer Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4207-7490","authenticated-orcid":false,"given":"Sarah P.","family":"Psutka","sequence":"additional","affiliation":[{"name":"Department of Urology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anish B.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Section, Division of Medical Oncology The Ohio State University Comprehensive Cancer Center \u2013 James Cancer Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjia","family":"Li","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Section, Division of Medical Oncology The Ohio State University Comprehensive Cancer Center \u2013 James Cancer Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine","family":"Collier","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Section, Division of Medical Oncology The Ohio State University Comprehensive Cancer Center \u2013 James Cancer Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Miah","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Section, Division of Medical Oncology The Ohio State University Comprehensive Cancer Center \u2013 James Cancer Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry V.","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Hinkley","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott S.","family":"Tykodi","sequence":"additional","affiliation":[{"name":"Division of Medical 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