{"doi":"10.1200/jco.20.03579","title":"Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non–Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study","abstract":"<jats:sec><jats:title>PURPOSE</jats:title><jats:p> Pembrolizumab monotherapy is standard first-line therapy for metastatic non–small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. </jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p> In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234 ), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P = .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; P = .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population. </jats:p></jats:sec>","journal":"Journal of Clinical Oncology","year":2021,"id":618909,"datarank":0.8323614127342831,"base_score":5.54907608489522,"endowment":5.54907608489522,"self_citation_contribution":0.8323614127342831,"citation_network_contribution":0.0,"self_endowment_contribution":0.8323614127342831,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":256,"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":1596939,"name":"Mehmet A. N. Şendur","orcid":null,"position":1,"is_corresponding":false},{"id":33778,"name":"Delvys Rodríguez‐Abreu","orcid":"0000-0003-0506-1366","position":2,"is_corresponding":false},{"id":13143,"name":"Keunchil Park","orcid":"0000-0002-4846-7449","position":3,"is_corresponding":false},{"id":244140,"name":"Dae Ho Lee","orcid":"0000-0002-9749-4638","position":4,"is_corresponding":false},{"id":1596943,"name":"Irfan Çiçin","orcid":"0000-0002-7584-3868","position":5,"is_corresponding":false},{"id":1596945,"name":"Perran Fulden Yumuk","orcid":"0000-0001-8650-299X","position":6,"is_corresponding":false},{"id":1596947,"name":"Francisco J. Orlandi","orcid":null,"position":7,"is_corresponding":false},{"id":434077,"name":"Ticiana Leal","orcid":"0000-0002-3735-9063","position":8,"is_corresponding":false},{"id":1596950,"name":"Olivier Molinier","orcid":"0000-0002-7965-2989","position":9,"is_corresponding":false},{"id":1596952,"name":"Nopadol Soparattanapaisarn","orcid":null,"position":10,"is_corresponding":false},{"id":1596954,"name":"Adrian Langleben","orcid":null,"position":11,"is_corresponding":false},{"id":917191,"name":"Raffaele Califano","orcid":"0000-0003-2611-5319","position":12,"is_corresponding":false},{"id":1596955,"name":"Balazs Medgyasszay","orcid":null,"position":13,"is_corresponding":false},{"id":1596956,"name":"Te-Chun Hsia","orcid":null,"position":14,"is_corresponding":false},{"id":230278,"name":"Gregory A. Otterson","orcid":"0000-0001-9877-8512","position":15,"is_corresponding":false},{"id":1247184,"name":"Lu Xu","orcid":"0000-0003-2753-4363","position":16,"is_corresponding":false},{"id":275512,"name":"Bilal Piperdi","orcid":"0000-0002-1315-3175","position":17,"is_corresponding":false},{"id":643814,"name":"Ayman Samkari","orcid":null,"position":18,"is_corresponding":false},{"id":616107,"name":"Martin Reck","orcid":"0000-0002-5336-9739","position":19,"is_corresponding":false},{"id":33769,"name":"Michael Boyer","orcid":"0000-0002-0452-2987","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non–Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study","abstract":"<jats:sec><jats:title>PURPOSE</jats:title><jats:p> Pembrolizumab monotherapy is standard first-line therapy for metastatic non–small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. </jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p> In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234 ), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P = .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; P = .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population. </jats:p></jats:sec>","is_dataset_classified":null,"base_score":5.54907608489522,"endowment":5.54907608489522,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33513313","pmcid":null,"openalex_id":"https://openalex.org/W3124587416","authors":[],"funders":[],"total_grants":0,"fwci":16.4625,"citation_percentile":0.99552989,"influential_citations":0,"citation_trend":[{"year":2021,"count":40},{"year":2022,"count":48},{"year":2023,"count":71},{"year":2024,"count":44},{"year":2025,"count":40},{"year":2026,"count":13}],"oa_status":"bronze","license":"other-oa","oa_locations":[{"url":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO.20.03579","host_type":"journal"},{"url":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO.20.03579","host_type":"publisher"},{"url":"https://doi.org/10.1200/jco.20.03579","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33513313","host_type":"repository"},{"url":"http://hdl.handle.net/10553/112553","host_type":"repository"},{"url":"https://hdl.handle.net/11424/243853","host_type":"repository"}],"fields_of_study":["Cancer Immunotherapy and Biomarkers","Peptidase Inhibition and Analysis","Lung Cancer Diagnosis and Treatment"],"mesh_terms":["Ipilimumab","Adult","Aged","Aged, 80 and over","Antineoplastic Combined Chemotherapy Protocols","Carcinoma, Non-Small-Cell Lung","Double-Blind Method","Female","Humans","Lung Neoplasms","Male","Middle Aged","B7-H1 Antigen","Antibodies, Monoclonal, Humanized"],"keywords":["Pembrolizumab","Ipilimumab","Medicine","Internal medicine","Placebo","Lung cancer","Hazard ratio","Population","Oncology","Adverse effect","Cancer","Surgery","Immunotherapy","Confidence interval","Pathology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T05:32:55.281066Z","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":[]}