{"doi":"10.1056/nejmoa1805453","title":"Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain","abstract":null,"journal":"New England Journal of Medicine","year":2018,"id":608189,"datarank":1.0796153031144888,"base_score":7.197435354096591,"endowment":7.197435354096591,"self_citation_contribution":1.0796153031144888,"citation_network_contribution":0.0,"self_endowment_contribution":1.0796153031144888,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1335,"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":1343917,"name":"Peter A. Forsyth","orcid":null,"position":1,"is_corresponding":false},{"id":1561911,"name":"Alain Algazi","orcid":null,"position":2,"is_corresponding":false},{"id":282233,"name":"Omid Hamid","orcid":"0000-0002-8238-4655","position":3,"is_corresponding":false},{"id":4541,"name":"F. Stephen Hodi","orcid":"0000-0001-6825-091X","position":4,"is_corresponding":false},{"id":548505,"name":"Stergios J. Moschos","orcid":"0000-0002-8943-0845","position":5,"is_corresponding":false},{"id":325115,"name":"Nikhil I. Khushalani","orcid":"0000-0002-3636-4143","position":6,"is_corresponding":false},{"id":1561914,"name":"Karl Lewis","orcid":null,"position":7,"is_corresponding":false},{"id":68918,"name":"Christopher D. Lao","orcid":null,"position":8,"is_corresponding":false},{"id":68931,"name":"Michael A. Postow","orcid":"0000-0002-3367-7961","position":9,"is_corresponding":false},{"id":288144,"name":"Michael B. 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Pavlick","orcid":"0000-0001-7088-0742","position":17,"is_corresponding":false},{"id":1561923,"name":"Joel Jiang","orcid":null,"position":18,"is_corresponding":false},{"id":1561925,"name":"Alexandre Avila","orcid":null,"position":19,"is_corresponding":false},{"id":1561926,"name":"Sheena Demelo","orcid":null,"position":20,"is_corresponding":false},{"id":325116,"name":"Kim Margolin","orcid":"0000-0002-5248-4356","position":21,"is_corresponding":false},{"id":90457,"name":"Hussein A. Tawbi","orcid":"0000-0003-1942-851X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain","abstract":"BACKGROUND: Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases. METHODS: In this open-label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response. RESULTS: Among 94 patients with a median follow-up of 14.0 months, the rate of intracranial clinical benefit was 57% (95% confidence interval [CI], 47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56% (95% CI, 46 to 67). Treatment-related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune-related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases. CONCLUSIONS: Nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. 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