{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:37:01Z","timestamp":1787017021406,"version":"build-2736575974"},"reference-count":25,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"unspecified","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,1,15]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitor (ICI)-based regimens can be associated with prolonged survival and disease control after treatment discontinuation without further anticancer therapy. An integrated, comprehensive partitioned survival analysis describes how patients spend overall survival (OS) time both on\/off treatment and with\/without toxicity. Previous analysis of first-line (1L) nivolumab+ipilimumab\u2009for advanced renal cell carcinoma (aRCC) in CheckMate 214 showed treatment-free survival (TFS; time between 1L and second-line (2L) therapies) was twice as long versus sunitinib. TFS and survival states for ICI plus vascular endothelial growth factor receptor-tyrosine kinase inhibitor are of interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In CheckMate 9ER, 651 randomized patients with aRCC received 1L nivolumab+cabozantinib\u2009or sunitinib. Minimum follow-up was 4 years. We partitioned area under the Kaplan-Meier OS curve into three survival states defined from randomization: time on 1L protocol therapy, TFS, and survival after 2L subsequent systemic therapy initiation. TFS and protocol therapy were subdivided into mean times with\/without grade 2+ treatment-related adverse events. Areas under and between Kaplan-Meier curves were estimated by 48-month restricted mean times to event. Bootstrapped 95% CIs for between-group differences are reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 4 years post-randomization, Kaplan-Meier OS estimates were 49.2% versus 40.2% with nivolumab+cabozantinib\u2009and sunitinib, respectively; 17.6% versus 4.7% of patients were in TFS; 15.8% versus 8.2% remained on 1L protocol therapy. The 48-month mean time on protocol therapy for nivolumab+cabozantinib versus sunitinib was 22.6 and 14.1\u2009months; 48-month mean TFS was 7.0 and 4.6\u2009months (difference, 2.4 (95% CI 0.8 to 3.9)); 48-month mean survival after 2L therapy initiation was 5.5 and 12.0\u2009months, respectively. The nivolumab+cabozantinib group spent 8.5 (95% CI 6.2 to 10.8)\u2009months more mean survival time on 1L protocol therapy, whereas the sunitinib group had 6.5 (95% CI 4.4 to 8.6)\u2009months more mean survival time after 2L therapy initiation. Both treatment groups spent at least half of TFS with grade 2+toxicity, resulting in a difference in mean TFS without toxicity of 0.7 (95% CI \u22120.4 to 1.8)\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Partitioned survival analysis over 4 years after initiation of 1L therapy for aRCC indicated that longer OS with nivolumab+cabozantinib versus sunitinib involved more time on 1L therapy and in TFS, and less survival time after 2L therapy initiation.<\/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=\"NCT03141177\">NCT03141177<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013546","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:35:17Z","timestamp":1769772917000},"page":"e013546","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Partitioned overall survival: comprehensive analysis of survival states over 4 years in CheckMate 9ER comparing first-line nivolumab plus cabozantinib versus sunitinib in advanced renal cell carcinoma"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03141177","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03141177","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Hollis","family":"Viray","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7672-3131","authenticated-orcid":false,"given":"Charlene","family":"M Mantia","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opeyemi A","family":"Jegede","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, 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 University Lombardi Comprehensive Cancer Center, Washington, DC, USA"}],"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\/0000-0002-9201-3217","authenticated-orcid":false,"given":"Toni K","family":"Choueiri","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F","family":"McDermott","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, 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, Massachusetts, USA"},{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"2026013003351242000_14.1.e013546.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026982"},{"key":"2026013003351242000_14.1.e013546.2","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S1470-2045(23)00049-9","article-title":"Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study","volume":"24","author":"Choueiri","year":"2023","journal-title":"Lancet Oncol"},{"key":"2026013003351242000_14.1.e013546.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1816714"},{"key":"2026013003351242000_14.1.e013546.4","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0008"},{"key":"2026013003351242000_14.1.e013546.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.05.537"},{"key":"2026013003351242000_14.1.e013546.6","doi-asserted-by":"crossref","DOI":"10.3390\/jcm13020307","article-title":"Navigating the ICI Combination Treatment Journey: Patterns of Response and Progression to First-Line ICI-Based Combination Treatment in Metastatic Renal Cell Carcinoma","volume":"13","author":"Samuelly","year":"2024","journal-title":"J Clin Med"},{"key":"2026013003351242000_14.1.e013546.7","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1200\/JCO.19.00345","article-title":"Treatment-Free Survival: A Novel Outcome Measure of the Effects of Immune Checkpoint Inhibition-A Pooled Analysis of Patients With Advanced Melanoma","volume":"37","author":"Regan","year":"2019","journal-title":"J Clin Oncol"},{"key":"2026013003351242000_14.1.e013546.8","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003743","article-title":"Treatment-free survival over extended follow-up of patients with advanced melanoma treated with immune checkpoint inhibitors in CheckMate 067","volume":"9","author":"Regan","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2026013003351242000_14.1.e013546.9","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-2283"},{"key":"2026013003351242000_14.1.e013546.10","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1200\/JCO.24.00279","article-title":"Metastasis-Free Survival Versus Treatment-Free Survival in Biochemically Recurrent Prostate Cancer: The EMBARK Trial","volume":"42","author":"Einstein","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026013003351242000_14.1.e013546.11","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-008293","article-title":"Treatment-free survival outcomes from the phase II study of nivolumab and salvage nivolumab\/ipilimumab in advanced clear cell renal cell carcinoma (HCRN GU16-260-Cohort A)","volume":"12","author":"Atkins","year":"2024","journal-title":"J Immunother Cancer"},{"key":"2026013003351242000_14.1.e013546.12","doi-asserted-by":"crossref","unstructured":"Zaemes J , Ari SL , Pascual L , et al . 1418\u2005Treatment-free survival in patients with advanced melanoma and non-small cell lung cancer receiving immune checkpoint inhibitors: real-world outcomes over a 3-year timespan. J Immunother Cancer 2023;A1576\u20137. doi:10.1136\/jitc-2023-SITC2023.1418","DOI":"10.1136\/jitc-2023-SITC2023.1418"},{"key":"2026013003351242000_14.1.e013546.13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/CMR.0000000000000793","article-title":"Sensitivity of treatment-free survival to subgroup analyses in patients with advanced melanoma treated with immune checkpoint inhibitors","volume":"32","author":"Mantia","year":"2022","journal-title":"Melanoma Res"},{"key":"2026013003351242000_14.1.e013546.14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"2026013003351242000_14.1.e013546.15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712126"},{"key":"2026013003351242000_14.1.e013546.16","doi-asserted-by":"crossref","DOI":"10.1136\/esmoopen-2020-001079","article-title":"Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial","volume":"5","author":"Albiges","year":"2020","journal-title":"ESMO Open"},{"key":"2026013003351242000_14.1.e013546.17","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-009495","article-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","volume":"12","author":"Mantia","year":"2024","journal-title":"J Immunother Cancer"},{"key":"2026013003351242000_14.1.e013546.18","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00290-X"},{"key":"2026013003351242000_14.1.e013546.19","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1200\/JCO.2024.42.4_suppl.362","article-title":"Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Results from 55-month follow-up of the CheckMate 9ER trial","volume":"42","author":"Bourlon","year":"2024","journal-title":"JCO"},{"key":"2026013003351242000_14.1.e013546.20","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2024.102994","article-title":"Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended follow-up from the phase III randomised CheckMate 9ER trial","volume":"9","author":"Powles","year":"2024","journal-title":"ESMO Open"},{"key":"2026013003351242000_14.1.e013546.21","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00693-8"},{"key":"2026013003351242000_14.1.e013546.22","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00318"},{"key":"2026013003351242000_14.1.e013546.23","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-023-02406-x"},{"key":"2026013003351242000_14.1.e013546.24","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1001\/jamaoncol.2021.0051","article-title":"Chronic Immune-Related Adverse Events Following Adjuvant Anti\u2013PD-1 Therapy for High-risk Resected Melanoma","volume":"7","author":"Patrinely","year":"2021","journal-title":"JAMA Oncol"},{"key":"2026013003351242000_14.1.e013546.25","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.1158\/1078-0432.CCR-23-3719","article-title":"A Pooled Analysis of Treatment-Free Survival in Advanced Renal Cell Carcinoma","volume":"30","author":"Chang","year":"2024","journal-title":"Clin Cancer Res"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-013546","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:35:20Z","timestamp":1769772920000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-013546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,30]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/jitc-2025-013546"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-013546","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}