{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:03:26Z","timestamp":1790276606266,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"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":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA\u2010approved as front\u2010line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off\u2010protocol and post\u2010front\u2010line experience with combination TKI\u2013IO approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective analysis of mRCC patients who received combination TKI\u2013IO post\u2010first\u2010line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 48 mRCC patients for inclusion: median age 65\u00a0years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI\u2013IO combinations included nivolumab\u2013cabozantinib (N\u00a0+C; 24 patients), nivolumab\u2013pazopanib (N+P; 13), nivolumab\u2013axitinib (6), nivolumab\u2013lenvatinib (2), and nivolumab\u2013ipilimumab\u2013cabozantinib (3). The median progression\u2010free survival was 11.6\u00a0months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n\u00a0=\u00a03, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade \u22653 adverse event.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To our knowledge, this is the first case series reporting off\u2010label use of combination TKI\u2013IO for mRCC. TKI\u2013IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.3812","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T06:55:00Z","timestamp":1614668100000},"page":"2341-2349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Combination antiangiogenic tyrosine kinase inhibition and anti\u2010PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9751-8188","authenticated-orcid":false,"given":"Andrew L.","family":"Laccetti","sequence":"first","affiliation":[{"name":"Genitourinary Oncology Service Department of Medicine Memorial Sloan Kettering Cancer Center New York NY 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