Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Issue 11 (21st April 2021)

• Record Type: Journal Article
• Authors: Tawbi, Hussein A; Forsyth, Peter A; Hodi, F Stephen; Lao, Christopher D; Moschos, Stergios J; Hamid, Omid; Atkins, Michael B; Lewis, Karl; Thomas, Reena P; Glaspy, John A; Jang, Sekwon; Algazi, Alain P; Khushalani, Nikhil I; Postow, Michael A; Pavlick, Anna C; Ernstoff, Marc S; Reardon, David A; Puzanov, Igor; Kudchadkar, Ragini R; Tarhini, Ahmad A; Sumbul, Anne; Rizzo, Jasmine I; Margolin, Kim A
• Is Part Of: Neuro-oncology. Volume 23:Issue 11(2021)
• Page Start: 1961
• Page End: 1973
• Publication Date: 2021-04-21
• Subjects: checkpoint inhibitor -- ipilimumab -- melanoma -- nivolumab -- symptomatic brain metastases; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noab094
• Languages: English
• ISSNs: 1522-8517

Abstract

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.