Flipped versus traditional nivolumab plus ipilimumab dosing in patients with melanoma brain metastases
In brief
Flipped nivolumab/ipilimumab dosing halves risk of death in melanoma brain metastases
In a retrospective Swedish cohort of 189 melanoma patients with brain mets, the flipped schedule (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) was linked to a 46% lower risk of death and a 44% lower risk of progression compared with the traditional schedule, while more patients completed all four induction doses and severe immune-related toxicity was modestly lower.
- Journal
- European journal of cancer (Oxford, England : 1990) (Q1)
- Published
- 10 September 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Karl Björkström, Anna Fager, Cissi Liu, Lars Ny, Hildur Helgadottir
- PMID
- 42743884
- DOI
- 10.1016/j.ejca.2026.117048
Why clinicians should know about it
- Picked for Dermatology (paper of the day, 17 September 2026): Flipped NIVO+IPI dosing improves OS in melanoma brain mets
Abstract
BACKGROUND: Nivolumab plus ipilimumab (NIVO+IPI) is a standard option for melanoma with brain metastases. "Flipped" dosing (nivolumab 3mg/kg + ipilimumab 1mg/kg; NIVO3 +IPI1) reduces toxicity relative to traditional dosing (nivolumab 1mg/kg + ipilimumab 3mg/kg; NIVO1 +IPI3) in extracranial disease, but its efficacy in patients with brain metastases is not established. PATIENTS AND METHODS: We retrospectively analyzed 189 patients with cutaneous,mucosal, acral or unknown-primary melanoma and brain metastases treated with NIVO + IPI at two Swedish university hospitals, comparing NIVO3 + IPI1 (n = 54) and NIVO1 + IPI3 (n = 135). Outcomes were treatment exposure, global, intracranial and extracranial objective response rate (ORR), progression free survival (PFS), overall survival (OS) and safety. OS and PFS were analysed using Cox regression adjusted for age, ECOG status, baseline LDH, brain disease burden and number of extracranial metastatic sites. RESULTS: Baseline characteristics were comparable, though local brain-directed therapy before NIVO + IPI was more frequent with flipped dosing (29.6% vs 14.8%, p = 0.019). More patients completed all four induction doses with flipped dosing (50.0% vs 30.4%, p = 0.011). Grade 3-4 immune-related adverse events occurred in 29.6% vs 43.0% (p = 0.090). Intracranial ORR was 44.4% vs 30.2% (p = 0.065), extracranial ORR 60.9% vs 53.4% (p = 0.409) and global ORR 42.6% vs 29.2% (p = 0.080). In adjusted analysis, flipped dosing was associated with longer PFS (aHR 0.56, 95% CI 0.38-0.83, p = 0.004) and OS (aHR 0.54, 95% CI 0.35-0.83, p = 0.005). CONCLUSION: In this real-world cohort of melanoma patients with brain metastases, flipped NIVO + IPI dosing was associated with more patients completing induction and longer OS and PFS. A prospective evaluation is warranted.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.