{"doi":"10.1056/nejmoa1504030","title":"Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma","abstract":"<h4>Background</h4>Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma.<h4>Methods</h4>We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here.<h4>Results</h4>The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group.<h4>Conclusions</h4>Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).","journal":"New England Journal of Medicine","year":2015,"id":7654,"datarank":13.95632752008721,"base_score":8.997889450200717,"endowment":8.997889450200717,"self_citation_contribution":1.3496834175301076,"citation_network_contribution":12.606644102557103,"self_endowment_contribution":1.3496834175301076,"citer_contribution":12.606644102557103,"corpus_percentile":89.7,"corpus_rank":1447,"citation_count":8085,"citer_count":144,"citers_with_citation_signal":144,"citers_with_endowment":144,"datacite_reuse_total":0,"is_dataset":false,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2015-07-02","authors":[{"id":68914,"name":"Vanna Chiarion-Sileni","orcid":null,"position":1,"is_corresponding":false},{"id":68915,"name":"Rene Gonzalez","orcid":null,"position":2,"is_corresponding":false},{"id":68916,"name":"Jean Jacques Grob","orcid":null,"position":3,"is_corresponding":false},{"id":68917,"name":"C. Lance Cowey","orcid":"0000-0001-8597-8486","position":4,"is_corresponding":false},{"id":68918,"name":"Christopher D. Lao","orcid":null,"position":5,"is_corresponding":false},{"id":5602,"name":"Dirk Schadendorf","orcid":"0000-0003-3524-7858","position":6,"is_corresponding":false},{"id":68919,"name":"Reinhard Dummer","orcid":"0000-0002-2279-6906","position":7,"is_corresponding":false},{"id":68920,"name":"Michael Smylie","orcid":"0000-0001-5945-0397","position":8,"is_corresponding":false},{"id":68921,"name":"Piotr Rutkowski","orcid":"0000-0002-8920-5429","position":9,"is_corresponding":false},{"id":68922,"name":"Pier F. Ferrucci","orcid":null,"position":10,"is_corresponding":false},{"id":37253,"name":"Andrew Hill","orcid":"0000-0001-8672-6379","position":11,"is_corresponding":false},{"id":68923,"name":"John Wagstaff","orcid":"0000-0002-1140-5981","position":12,"is_corresponding":false},{"id":68924,"name":"Matteo S. Carlino","orcid":"0000-0002-7861-4104","position":13,"is_corresponding":false},{"id":68925,"name":"John B. Haanen","orcid":null,"position":14,"is_corresponding":false},{"id":68926,"name":"Michele Maio","orcid":"0000-0002-0323-6321","position":15,"is_corresponding":false},{"id":68927,"name":"Ivan Marquez-Rodas","orcid":null,"position":16,"is_corresponding":false},{"id":68928,"name":"Grant A. McArthur","orcid":"0000-0001-8908-6071","position":17,"is_corresponding":false},{"id":68929,"name":"Paolo A. Ascierto","orcid":"0000-0002-8322-475X","position":18,"is_corresponding":false},{"id":13750,"name":"Georgina V. Long","orcid":"0000-0001-8894-3545","position":19,"is_corresponding":false},{"id":68930,"name":"Margaret K. Callahan","orcid":"0000-0002-9087-0012","position":20,"is_corresponding":false},{"id":68931,"name":"Michael A. Postow","orcid":"0000-0002-3367-7961","position":21,"is_corresponding":false},{"id":68932,"name":"Kenneth Grossmann","orcid":null,"position":22,"is_corresponding":false},{"id":68933,"name":"Mario Sznol","orcid":"0000-0002-4359-8749","position":23,"is_corresponding":false},{"id":68934,"name":"Brigitte Dreno","orcid":null,"position":24,"is_corresponding":false},{"id":68935,"name":"Lars Bastholt","orcid":"0000-0001-5478-9826","position":25,"is_corresponding":false},{"id":68936,"name":"Arvin Yang","orcid":null,"position":26,"is_corresponding":false},{"id":68937,"name":"Linda M. Rollin","orcid":null,"position":27,"is_corresponding":false},{"id":68938,"name":"Christine Horak","orcid":null,"position":28,"is_corresponding":false},{"id":4541,"name":"F. Stephen Hodi","orcid":"0000-0001-6825-091X","position":29,"is_corresponding":false},{"id":3666,"name":"Jedd D. Wolchok","orcid":"0000-0001-6718-2222","position":30,"is_corresponding":false},{"id":68939,"name":"Vanna Chiarion‐Sileni","orcid":"0000-0001-9191-9124","position":31,"is_corresponding":false},{"id":68940,"name":"René González","orcid":"0000-0002-7435-6208","position":32,"is_corresponding":false},{"id":68941,"name":"Jean‐Jacques Grob","orcid":"0000-0002-0667-153X","position":33,"is_corresponding":false},{"id":68942,"name":"Pier Francesco Ferrucci","orcid":"0000-0001-6255-5851","position":34,"is_corresponding":false},{"id":68943,"name":"John B.A.G. Haanen","orcid":"0000-0001-5884-7704","position":35,"is_corresponding":false},{"id":68944,"name":"Iván Márquez‐Rodas","orcid":"0000-0002-2476-668X","position":36,"is_corresponding":false},{"id":68945,"name":"Kenneth F. Grossmann","orcid":"0000-0002-8523-7407","position":37,"is_corresponding":false},{"id":68946,"name":"Brigitte Dréno","orcid":"0000-0001-5574-5825","position":38,"is_corresponding":false},{"id":68947,"name":"Christine E. Horak","orcid":null,"position":39,"is_corresponding":false},{"id":68913,"name":"James Larkin","orcid":"0000-0001-5569-9523","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}