Ipilimumab plus nivolumab ‘considered a cure’ long term for melanoma brain metastasis
Key takeaways:
- The 7-year intracranial progression free-survival among patients treated with combination therapy was 42%.
- Similarly, 48% of those patients achieved a 7-year overall survival.
Seven-year follow-up data of a multicenter, randomized phase 2 study evaluating the treatment of melanoma brain metastases shows ipilimumab plus nivolumab is an effective long-term care option.
First published in 2018, results from the Anti-PD-1 Brain Collaboration (ABC) trial showed that intracranial ipilimumab plus nivolumab treatment could slow the progression of melanoma brain metastases — a finding that “changed practice overnight” according to Georgina V. Long, PhD, MBBS, FRACP, AAHMS, professor at the University of Sydney, comedical director of Melanoma Institute Australia and chair of melanoma medical oncology and translational research at Melanoma Institute Australia and Royal North Shore Hospital.
“First-line combination immunotherapy with nivolumab and ipilimumab became the standard of care for patients with stage 4 melanoma and active metastases,” Long told Healio, after results from the ABC trial in 2018 reported a 46% intracranial response rate with ipilimumab plus nivolumab in patients with active asymptomatic melanoma brain metastases vs. 20% in those who receive nivolumab alone.
In the trial, 79 patients with active asymptomatic melanoma brain metastases were randomly assigned to cohort A (n = 36), cohort B (n = 27) or cohort C (n = 16). In cohort A, patients received IV ipilimumab 3 mg/kg plus nivolumab 1 mg/kg every 3 weeks for four doses, then nivolumab 3 mg/kg every 2 weeks. In cohort B, patients were treated with IV nivolumab 3 mg/kg every 2 weeks. Cohort C was composed of patients with previous brain-directed therapy, neurological symptoms or leptomeningeal disease who nonrandomly received IV nivolumab 3 mg/kg every 2 weeks.
After conducting this follow-up study of the ABC trial to evaluate the long-term efficacy of this combination treatment for asymptomatic melanoma brain metastases, Long and colleagues discovered a large proportion of patients survived another 7 years — a stark contrast to the median overall survival of 4 to 5 months before the discovery of this regimen.
In cohort A, 51% (95% CI, 34%-69%) achieved an overall intracranial response compared with 20% (95% CI, 7%-41%) and 6% (95% CI, 0%-30%) in cohort B and C, respectively.
The 7-year intracranial progression-free survival was 42% (95% CI, 29%-63%), 15% (95% CI, 6%-39%) and 6% (95% CI, 1%-42%) in cohorts A, B and C, respectively. Similarly, the 7-year overall survival was 48% (95% CI, 34%-68%), 26% (95% CI, 13%-51%) and 13% (95% CI, 3%-46%) in the respective cohorts.
According to the study, the safety results were consistent with the original analysis, with deaths occurring in 51%, 72% and 88% of cohorts A, B and C, respectively.
“Patients with stage 4 metastatic melanoma with active brain metastases can have long-term durable control of their melanoma beyond 7 years,” Long said. “This could be considered a ‘cure.’”