{"doi":"10.1136/jitc-2023-008293","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)","abstract":"BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Nivolumab monotherapy with salvage nivolumab/ipilimumab in non-responders is an active treatment approach in treatment-naïve 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.","journal":"Journal for ImmunoTherapy of Cancer","year":2024,"id":446624,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9362,"is_data_producer":false,"deposit_databanks":null,"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. Jegede","orcid":"0000-0003-1763-8214","position":1,"is_corresponding":false},{"id":560133,"name":"Naomi B. Haas","orcid":"0000-0001-8907-7968","position":2,"is_corresponding":false},{"id":95252,"name":"David F. McDermott","orcid":"0000-0002-2675-5095","position":3,"is_corresponding":false},{"id":105141,"name":"Mehmet Asım Bilen","orcid":"0000-0003-4003-1103","position":4,"is_corresponding":false},{"id":263637,"name":"Mark N. Stein","orcid":"0000-0002-0853-3640","position":5,"is_corresponding":false},{"id":232507,"name":"Jeffrey A. Sosman","orcid":"0000-0002-0650-9698","position":6,"is_corresponding":false},{"id":1165849,"name":"Robert Alter","orcid":null,"position":7,"is_corresponding":false},{"id":226676,"name":"Elizabeth R. Plimack","orcid":"0000-0002-7618-0744","position":8,"is_corresponding":false},{"id":686451,"name":"Moshe Chaim Ornstein","orcid":"0000-0003-0184-3467","position":9,"is_corresponding":false},{"id":854419,"name":"Michael E. Hurwitz","orcid":"0000-0002-1326-7308","position":10,"is_corresponding":false},{"id":258329,"name":"David Peace","orcid":"0000-0002-9403-760X","position":11,"is_corresponding":false},{"id":445670,"name":"David J. Einstein","orcid":"0000-0001-9163-3281","position":12,"is_corresponding":false},{"id":274716,"name":"Paul J. Catalano","orcid":"0000-0002-1105-8852","position":13,"is_corresponding":false},{"id":232505,"name":"Hans J. Hammers","orcid":"0000-0002-6224-4559","position":14,"is_corresponding":false},{"id":406334,"name":"Meredith M. Regan","orcid":"0000-0002-2428-6109","position":15,"is_corresponding":false},{"id":288144,"name":"Michael B. Atkins","orcid":"0000-0003-3901-9924","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:54.980444Z","pmid":"38604810","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":[]}