{"doi":"10.1136/jitc-2024-009495","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","abstract":"BACKGROUND: 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. METHODS: 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. RESULTS: At 5 years from randomization, 48% of patients treated with NIVO+IPI and 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% CI 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% CI 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. CONCLUSIONS: 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. TRIAL REGISTRATION NUMBER: NCT02231749.","journal":"Journal for ImmunoTherapy of Cancer","year":2024,"id":425618,"datarank":0.6147355051426374,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.16537566410953872,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.16537566410953872,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":16,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02231749"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":274715,"name":"Opeyemi A. 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Rini","orcid":"0000-0002-2212-080X","position":10,"is_corresponding":false},{"id":232505,"name":"Hans J. Hammers","orcid":"0000-0002-6224-4559","position":11,"is_corresponding":false},{"id":91584,"name":"Bernard Escudier","orcid":"0000-0002-4626-0479","position":12,"is_corresponding":false},{"id":91592,"name":"Laurence Albigès","orcid":"0000-0002-5734-3480","position":13,"is_corresponding":false},{"id":593793,"name":"Lisa Rosenblatt","orcid":null,"position":14,"is_corresponding":false},{"id":288144,"name":"Michael B. Atkins","orcid":"0000-0003-3901-9924","position":15,"is_corresponding":false},{"id":406334,"name":"Meredith M. Regan","orcid":"0000-0002-2428-6109","position":16,"is_corresponding":false},{"id":95252,"name":"David F. McDermott","orcid":"0000-0002-2675-5095","position":17,"is_corresponding":false},{"id":673439,"name":"Charlene Mantia","orcid":"0000-0001-7672-3131","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:58:32.160975Z","pmid":"39060019","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}