{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:14:12Z","timestamp":1793070852571,"version":"4.5.0"},"reference-count":31,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"unspecified","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,7,4]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of therapy. Treatment-free survival (TFS) with and without toxicity as a component of a partitioned survival model can characterize patient survival time, which is not captured by standard outcome measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from 1096 patients with advanced renal cell carcinoma treated with first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the CheckMate 214 trial were analyzed. TFS was defined as the area between two Kaplan-Meier curves for time from randomization to protocol therapy discontinuation and time from randomization to subsequent systemic therapy initiation or death, estimated as the difference in 60-month restricted mean times with confidence intervals (CIs) obtained using bootstrap sampling. Time on protocol therapy and TFS were further characterized as time with and without grade 2+ and 3+TRAEs. Survival functions were estimated in subgroups including International Metastatic Renal Cell Carcinoma Database Consortium risk groups using the Kaplan-Meier method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 5 years from randomization, 48% of patients treated with NIVO+IPI\u2009and 37% of patients treated with SUN were alive. In the intent-to-treat population, 18% of the NIVO+IPI-treated and 5% of SUN-treated patients are surviving treatment-free. For favorable-risk patients, the 60-month mean TFS was 14.4 months for NIVO+IPI versus 5.5 months for SUN (difference 8.9 months (95%\u2009CI 4.9 to 12.8)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 5.0 and 2.1 months, respectively, and with grade 3+TRAEs was 1.2 and 0.3 months, respectively. For intermediate\/poor-risk patients, the 60-month mean TFS was 10.1 months for NIVO+IPI versus 4.1 months for SUN (difference 6.1 months (95%\u2009CI 4.2 to 7.9)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 4.0 versus 2.0 months, respectively, and 0.6 versus 0.3 months with grade 3+TRAEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although overall survival was similar, favorable-risk patients treated with NIVO+IPI spent more time surviving treatment-free with and without toxicity versus SUN after 60 months of follow-up. Intermediate\/poor-risk patients treated with NIVO+IPI had longer survival and longer TFS without toxicity versus SUN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02231749\">NCT02231749<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2024-009495","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T01:41:11Z","timestamp":1721958071000},"page":"e009495","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct02231749","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7672-3131","authenticated-orcid":false,"given":"Charlene M","family":"Mantia","sequence":"first","affiliation":[{"name":"Harvard Medical School, Boston, Massachussetts, USA"},{"name":"Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opeyemi A","family":"Jegede","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R","family":"Plimack","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Fox Chase Cancer Center, Temple Health, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Powles","sequence":"additional","affiliation":[{"name":"Department of Urology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6925-2327","authenticated-orcid":false,"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":"Nizar M","family":"Tannir","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Han","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Urology, Department of Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0551-5807","authenticated-orcid":false,"given":"Martin H","family":"Voss","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9201-3217","authenticated-orcid":false,"given":"Toni K","family":"Choueiri","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachussetts, USA"},{"name":"Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2212-080X","authenticated-orcid":false,"given":"Brian I","family":"Rini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J","family":"Hammers","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Escudier","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Albig\u00e8s","sequence":"additional","affiliation":[{"name":"Department of Cancer Medicine, Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Rosenblatt","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-9924","authenticated-orcid":false,"given":"Michael B","family":"Atkins","sequence":"additional","affiliation":[{"name":"Georgetown-Lombardi Comprehensive Cancer Center, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2428-6109","authenticated-orcid":false,"given":"Meredith M","family":"Regan","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachussetts, USA"},{"name":"Division of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F","family":"McDermott","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachussetts, USA"},{"name":"Division of Medical Oncology, Beth Israel Deaconess Medical Center, Dana Farber\/Harvard Cancer Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"2025100306025166000_12.7.e009495.1","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1158\/1078-0432.CCR-21-3238","article-title":"From basic science to clinical translation in kidney cancer: a report from the second kidney cancer research summit","volume":"28","author":"Choueiri","year":"2022","journal-title":"Clin Cancer 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