{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:00:59Z","timestamp":1788415259133,"version":"build-2803163510"},"reference-count":17,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"unspecified","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NCI P30 CA051008"],"award-info":[{"award-number":["NCI P30 CA051008"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NCI P50CA101942"],"award-info":[{"award-number":["NCI P50CA101942"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"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":[[2024,3,11]]},"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>As part of a partitioned survival analysis, treatment-free survival (TFS) can characterize the overall survival time patients spend between the cessation of immunotherapy and the start of subsequent therapy; both with and without toxicity. Significant TFS was reported for the nivolumab\/ipilimumab arms of the CheckMate 067 and 214 trials for patients with advanced melanoma or renal cell carcinoma (aRCC), respectively, where immunotherapy was often halted for toxicity rather than a predefined treatment endpoint. We therefore sought to assess TFS in the HCRN GU16-260 trial, which was designed to reduce toxicity and cap immunotherapy duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data were analyzed from 128 patients with clear-cell aRCC treated with first-line nivolumab monotherapy for up to 2 years. Salvage nivolumab\/ipilimumab for up to 1 year was provided to eligible patients with disease progression at any point or stable disease at 48 weeks (29% of patients). TFS was defined as the area between Kaplan-Meier curves for a time from registration to protocol therapy cessation and for a time from registration to subsequent systemic therapy initiation or death, estimated from 36-month mean times. The time on or off protocol treatment with grade 3+treatment-related adverse events (TRAEs) was also captured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 36 months from enrollment, 68.3% of patients were alive: 96.8% of International Metastatic RCC Database Consortium (IMDC) favorable-risk patients and 56.6% of those with intermediate\/poor-risk, respectively. The 36-month mean time on protocol therapy was 11.5 months including 0.6 months with grade 3+TRAEs (16.0 months for favorable-risk patients and 9.6 months for intermediated\/poor-risk patients). The 36-month mean TFS for the whole population was 9.4 months (12.9 months including 1.5 months with grade 3+TRAEs for favorable-risk and 8.0 months including 1.0 months with grade 3+TRAEs for intermediate\/poor-risk). At 36 months, 65.6% of favorable-risk patients and 27.1% of intermediate\/poor-risk patients were alive and subsequent systemic treatment-free.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Nivolumab monotherapy with salvage nivolumab\/ipilimumab in non-responders is an active treatment approach in treatment-na\u00efve patients with aRCC and, similar to nivolumab\/ipilimumab in CheckMate 214, results in substantial TFS and toxicity-free TFS. TFS was greatest in patients with favorable-risk disease, supporting the use of an immunotherapy-only regimen in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2023-008293","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T22:30:14Z","timestamp":1712874614000},"page":"e008293","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"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)"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-9924","authenticated-orcid":false,"given":"Michael B","family":"Atkins","sequence":"first","affiliation":[{"name":"Oncology, Georgetown University Medical Center, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opeyemi A","family":"Jegede","sequence":"additional","affiliation":[{"name":"Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi B","family":"Haas","sequence":"additional","affiliation":[{"name":"Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F","family":"Mcdermott","sequence":"additional","affiliation":[{"name":"Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4003-1103","authenticated-orcid":false,"given":"Mehmet A","family":"Bilen","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stein","sequence":"additional","affiliation":[{"name":"Columbia University, New York, New York, USA"},{"name":"Columbia University\/Herbert Irving Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Sosman","sequence":"additional","affiliation":[{"name":"Northwestern University Department of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Alter","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R","family":"Plimack","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0184-3467","authenticated-orcid":false,"given":"Moshe C","family":"Ornstein","sequence":"additional","affiliation":[{"name":"Taussig Cancer Institute, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hurwitz","sequence":"additional","affiliation":[{"name":"Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Peace","sequence":"additional","affiliation":[{"name":"Medicine, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-3281","authenticated-orcid":false,"given":"David","family":"Einstein","sequence":"additional","affiliation":[{"name":"Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Catalano","sequence":"additional","affiliation":[{"name":"Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hammers","sequence":"additional","affiliation":[{"name":"The University of Texas Southwestern Medical Center, Dallas, Texas, 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":"Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,4,11]]},"reference":[{"key":"2025100314570860000_12.4.e008293.1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003743","article-title":"Treatment-free survival 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