Ipilimumab/Nivolumab versus Nivolumab in Melanoma Brain Metastases

1. Intracranial objective response rate was 51% with ipilimumab plus nivolumab and 20% with nivolumab alone.

2. Treatment-related grade 3 or higher adverse events occurred in 54% with ipilimumab plus nivolumab, and 20% with nivolumab alone.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Brain metastases occur in 30–40% of melanoma patients at stage IV diagnosis, and previous trials demonstrated a moderate intracranial response rate with ipilimumab plus nivolumab in patients with active asymptomatic melanoma brain metastases, setting a new standard of care. This trial assessed the long-term efficacy and safety of ipilimumab plus nivolumab versus nivolumab in patients with melanoma brain metastases. The primary endpoint was intracranial objective response rate (ORR) and secondary endpoints included intracranial progression-free survival (PFS), extracranial PFS, overall survival (OS), and safety. Intracranial ORR was 51% cohort A with 26% being complete response and 20% from cohort B with 16% being a complete response. Extracranial ORR was 57% in cohort A and 29% in cohort B. In cohort C, 6% had an intracranial response (complete response) and 25% had an extracranial response (two complete responses and one partial response). Median intracranial PFS was 5.4 months in cohort A, 2.5 months in cohort B, and 2.3 months in cohort C. 7-year extracranial PFS was 46% in cohort A and 21% in cohort B. Median OS was 64.1 months in cohort A and 26.2 months in cohort B. With regard to safety, 54% patients in cohort A, 20% in cohort B, and 13% in cohort C had treatment-related grade 3 or higher adverse events. The strengths of this study included its methodology and the limitations included the sample size. Overall, it was found that ipilimumab plus nivolumab show some improved outcomes in patients with melanoma brain metastases.

Click to read the study in Lancet Oncology

Relevant Reading: Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain

In-Depth [randomized controlled trial]: This Australian, open-label, phase 2 study enrolled adults with stage IV melanoma who have at least 1 active intracranial lesion seen on MRI and no previous brain-directed therapy and then randomized them (5:4) into cohort A (3mg/kg ipilimumab plus 1mg/kg nivolumab, followed by 3mg/kg nivolumab consolidation, n=36) or cohort B (3mg/kg nivolumab, n=27). Those who had previous brain-directed therapy were enrolled without randomization to cohort C (3mg/kg nivolumab, n=16). Median follow-up was 7.6 years. Intracranial ORR was 51% (95%CI, 34-69) cohort A with 26% being complete response and 20% (95%CI, 7-41) from cohort B with 16% being a complete response. Extracranial ORR was 57% (95%CI, 37-75) in cohort A and 29% (95%CI, 11-52) in cohort B. In cohort C, 6% (95%CI, 0-30) had an intracranial response (complete response) and 25% (95%CI, 5-57) had an extracranial response (two complete responses and one partial response). Median intracranial PFS was 5.4 months (95%CI, 2.7–NA) in cohort A, 2.5 months (95%CI, 1.7-2.8) in cohort B, and 2.3 months (95%CI, 1.4-4.3) in cohort C. 7-year extracranial PFS was 46% (95%CI, 31-68) in cohort A and 21% (95%CI, 9-50) in cohort B. Median OS was 64.1 months (95%CI, 11.9-NA) in cohort A and 26.2 months (95%CI, 7.0-NA) in cohort B. In regard to safety, 54% patients in cohort A, 20% in cohort B, and 13% in cohort C had treatment-related grade 3 or higher adverse events. Overall, it was found that ipilimumab plus nivolumab show some improved outcomes in patients with melanoma brain metastases.

Image: PD

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