{"doi":"10.1093/oncolo/oyad298","title":"A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>Nivolumab plus ipilimumab has demonstrated improved survival for treatment-naïve advanced clear cell renal cell carcinoma (RCC). A series of clinical trials evaluated the effect of salvage nivolumab plus ipilimumab in patients without an objective response to nivolumab. Given the size and heterogeneity of these studies, we performed a pooled analysis to better inform the activity of nivolumab plus ipilimumab after nivolumab.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and Methods</jats:title>\n                  <jats:p>Eligible patients included those with advanced clear cell RCC having received no prior immunotherapy. The primary objective was confirmed objective response rate (ORR) by investigator-assessment. Secondary objectives included progression-free survival (PFS) and overall survival (OS).</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>The analysis included 410 patients with clear cell RCC, of whom 340 (82.9%) had IMDC intermediate/poor risk disease, and 137 (33.4%) had prior treatment. The 16-18-week ORR to nivolumab prior to nivolumab plus ipilimumab was 22.7% (n = 93), and best ORR to nivolumab was 25.1% (n = 103). Two hundred and thirty (56.1%) patients treated with nivolumab received nivolumab plus ipilimumab at a median of 16 weeks (IQR 9-19) after initiation of nivolumab [27.0% (n = 62) with stable disease and 73.0% (n = 168) with progressive disease to nivolumab]. The ORR to nivolumab plus ipilimumab was 12.6% (n = 29). Six-month PFS on nivolumab plus ipilimumab was 37% (95% CI, 27-47). Median follow-up was 34.3 months and 3-year OS was 59% (95% CI, 53-64) from nivolumab start.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>A small subset of patients lacking a response to nivolumab derive benefit from salvage nivolumab plus ipilimumab. When possible, both drugs should be given in concomitantly, rather in an adaptive fashion.</jats:p>\n               </jats:sec>","journal":"The Oncologist","year":2024,"id":597143,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1529730,"name":"Katharina Leucht","orcid":null,"position":1,"is_corresponding":false},{"id":274682,"name":"Wanling Xie","orcid":"0000-0001-5995-8000","position":2,"is_corresponding":false},{"id":1529732,"name":"Opeyemi Jegede","orcid":null,"position":3,"is_corresponding":false},{"id":1529734,"name":"David A Braun","orcid":null,"position":4,"is_corresponding":false},{"id":288144,"name":"Michael B. Atkins","orcid":"0000-0003-3901-9924","position":5,"is_corresponding":false},{"id":1529737,"name":"Marc-Oliver Grimm","orcid":null,"position":6,"is_corresponding":false},{"id":16405,"name":"Toni K. Choueiri","orcid":"0000-0002-9201-3217","position":7,"is_corresponding":false},{"id":1529728,"name":"Rana R McKay","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>Nivolumab plus ipilimumab has demonstrated improved survival for treatment-naïve advanced clear cell renal cell carcinoma (RCC). A series of clinical trials evaluated the effect of salvage nivolumab plus ipilimumab in patients without an objective response to nivolumab. Given the size and heterogeneity of these studies, we performed a pooled analysis to better inform the activity of nivolumab plus ipilimumab after nivolumab.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and Methods</jats:title>\n                  <jats:p>Eligible patients included those with advanced clear cell RCC having received no prior immunotherapy. The primary objective was confirmed objective response rate (ORR) by investigator-assessment. Secondary objectives included progression-free survival (PFS) and overall survival (OS).</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>The analysis included 410 patients with clear cell RCC, of whom 340 (82.9%) had IMDC intermediate/poor risk disease, and 137 (33.4%) had prior treatment. The 16-18-week ORR to nivolumab prior to nivolumab plus ipilimumab was 22.7% (n = 93), and best ORR to nivolumab was 25.1% (n = 103). Two hundred and thirty (56.1%) patients treated with nivolumab received nivolumab plus ipilimumab at a median of 16 weeks (IQR 9-19) after initiation of nivolumab [27.0% (n = 62) with stable disease and 73.0% (n = 168) with progressive disease to nivolumab]. The ORR to nivolumab plus ipilimumab was 12.6% (n = 29). Six-month PFS on nivolumab plus ipilimumab was 37% (95% CI, 27-47). Median follow-up was 34.3 months and 3-year OS was 59% (95% CI, 53-64) from nivolumab start.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>A small subset of patients lacking a response to nivolumab derive benefit from salvage nivolumab plus ipilimumab. When possible, both drugs should be given in concomitantly, rather in an adaptive fashion.</jats:p>\n               </jats:sec>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37950901","pmcid":"PMC10994246","openalex_id":"https://openalex.org/W4388586239","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"T32 CA009172","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR001863","title":null},{"funder_name":"National Institutes of Health","grant_id":"2P50CA101942-16","title":"DF/HCC Kidney Cancer SPORE"},{"funder_name":"National Institutes of Health","grant_id":"5P30CA006516-56","title":"Dana-Farber/Harvard Cancer Center"},{"funder_name":"Bristol-Myers Squibb","grant_id":"","title":null}],"total_grants":5,"fwci":0.835,"citation_percentile":0.74173307,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://academic.oup.com/oncolo/advance-article-pdf/doi/10.1093/oncolo/oyad298/53253478/oyad298.pdf","host_type":"journal"},{"url":"https://academic.oup.com/oncolo/advance-article-pdf/doi/10.1093/oncolo/oyad298/53253478/oyad298.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/oncolo/article-pdf/29/4/324/57210351/oyad298.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/oncolo/oyad298","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37950901","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10994246","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10994246/pdf/oyad298.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10994246","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10994246?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1093/oncolo/oyad298","host_type":""}],"fields_of_study":["Renal cell carcinoma treatment","Cancer Immunotherapy and Biomarkers","Ferroptosis and cancer prognosis","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Ipilimumab","Nivolumab","Progression-Free Survival","Antineoplastic Combined Chemotherapy Protocols","Carcinoma, Renal Cell","Humans","Kidney Neoplasms","Clinical Trials, Phase II as Topic"],"keywords":["Nivolumab","Ipilimumab","Medicine","Renal cell carcinoma","Internal medicine","Oncology","Immunotherapy","Cancer","Response","Adaptive","Genitourinary Cancer","Clinical Trials, Phase II as Topic","Antineoplastic Combined Chemotherapy Protocols","Humans","Carcinoma, Renal Cell","Kidney Neoplasms","Progression-Free Survival"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"No poverty"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T12:23:18.570584Z","pmid":null,"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":[]}