{"doi":"10.1093/neuonc/noab094","title":"Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204)","abstract":"BACKGROUND: In patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%. Here, we present the first report for patients who were symptomatic and/or required corticosteroids and updated data for asymptomatic patients. METHODS: Patients with measurable MBM, 0.5-3.0 cm, were enrolled into Cohort A (asymptomatic) or Cohort B (stable neurologic symptoms and/or receiving corticosteroids). Nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg, were given intravenously every 3 weeks ×4, followed by nivolumab, 3 mg/kg, every 2 weeks until progression, unacceptable toxicity, or 24 months. The primary endpoint was intracranial clinical benefit rate (CBR; complete response [CR], partial response [PR], or stable disease ≥6 months). RESULTS: Symptomatic patients (N = 18) received a median of one nivolumab and ipilimumab combination dose and had an intracranial CBR of 22.2%. Two of 12 patients on corticosteroids had CR; 2 responded among the 6 not on corticosteroids. Median intracranial progression-free survival (PFS) and overall survival (OS) were 1.2 and 8.7 months, respectively. In contrast, with 20.6 months of follow-up, we confirmed an intracranial CBR of 58.4% in asymptomatic patients (N = 101); median duration of response, PFS, and OS were not reached. No new safety signals were observed. CONCLUSIONS: Nivolumab plus ipilimumab provides durable clinical benefit for asymptomatic patients with MBM and should be considered for first-line therapy. This regimen has limited activity in MBM patients with neurologic symptoms and/or requiring corticosteroids, supporting the need for alternative approaches and methods to reduce the dependency on corticosteroids. Clinical trial registration. ClinicalTrials.gov, NCT02320058.","journal":"Neuro-Oncology","year":2021,"id":148459,"datarank":4.011400952156029,"base_score":4.844187086458591,"endowment":4.844187086458591,"self_citation_contribution":0.7266280629687888,"citation_network_contribution":3.2847728891872396,"self_endowment_contribution":0.7266280629687888,"citer_contribution":3.2847728891872396,"corpus_percentile":null,"corpus_rank":null,"citation_count":126,"citer_count":91,"citers_with_citation_signal":77,"citers_with_endowment":77,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.884,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02320058"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":225601,"name":"Peter Forsyth","orcid":"0000-0002-3756-8594","position":1,"is_corresponding":false},{"id":4541,"name":"F. 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