As reported in The Lancet Oncology by Long et al, 7-year follow-up of the Australian phase II ABC trial showed continued benefit of ipilimumab/nivolumab vs nivolumab alone in patients with asymptomatic melanoma brain metastases.
Study Details
In the open-label multicenter study, 63 immunotherapy-naive patients with asymptomatic metastases and no prior brain-directed therapy were randomly assigned 5:4 to receive ipilimumab/nivolumab (n = 36) or nivolumab alone (n = 27). An additional 16 patients with previous brain-directed therapy, neurologic symptoms, or leptomeningeal disease were assigned to receive nivolumab alone. Patients in the combination group received four doses of ipilimumab at 3 mg/kg plus nivolumab at 1 mg/kg every 3 weeks over 12 weeks, followed by nivolumab at 3 mg/kg every 2 weeks. Patients in the nivolumab group and the nonrandomized group received nivolumab at 3 mg/kg every 2 weeks. Maintenance nivolumab was changed to 480 mg every 4 weeks in a protocol amendment. Treatment continued until disease progression or unacceptable toxicity.
Key Findings
Median follow-up was 7.6 years. Intracranial responses occurred in 51% of the combination group, 20% of the nivolumab-alone group, and 6% of the nonrandomized nivolumab group.
Intracranial progression-free survival at 7 years was 42% (95% confidence interval [CI] = 29%–63%) in the combination group, 15% (95% CI = 6%–39%) in the nivolumab group, and 6% (95% CI = 1%–42%) in the nonrandomized nivolumab group. Overall survival rate at 7 years was 48% (95% CI = 34%–68%), 26% (95% CI = 13%–51%), and 13% (95% CI = 3%–46%) in the three groups, respectively.
The investigators concluded: “Our findings suggest that ipilimumab plus nivolumab maintains efficacy to at least 7 years in patients with active asymptomatic brain metastasis. Upfront ipilimumab plus nivolumab should be the standard of care for patients with melanoma brain metastasis; a trial investigating the role of stereotactic surgery in this new paradigm is ongoing.”
Georgina V. Long, PhD, MBBS, of the Melanoma Institute Australia, University of Sydney, Sydney, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the Melanoma Institute Australia and Bristol Myers Squibb. For full disclosures of all study authors, visit The Lancet Oncology.
