Nivolumab/Ipilimumab or Nivolumab Alone in Melanoma Brain Metastases
In an Australian phase II trial reported in The Lancet Oncology, Long et al found that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) and nivolumab alone showed intracranial activity in patients with melanoma brain metastases.
Study Details
In the open-label trial, 76 evaluable patients from 4 sites in Australia were enrolled into 3 cohorts between November 2014 and April 2017. Patients with asymptomatic brain metastases with no previous local brain therapy were randomized to 2 cohorts: cohort A (n = 35) received nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg every 3 weeks for 4 doses followed by nivolumab at 3 mg/kg every 2 weeks; and cohort B (n = 25) received nivolumab at 3 mg/kg every 2 weeks. Patients with brain metastases with local therapy failure or with neurologic symptoms or leptomeningeal disease were enrolled into the nonrandomized cohort C (n = 16) and treated with nivolumab at 3 mg/kg every 2 weeks.
The primary endpoint was intracranial response at or after week 12.
Intracranial Activity
At data cutoff in August 2017, with a median follow-up of 17 months, intracranial responses were observed in 16 patients (46%) in cohort A, 5 patients (20%) in cohort B, and 1 patient (6%) in cohort C. Intracranial complete responses were observed in 6 patients (17%), 3 patients (12%), and no patients in cohorts A, B, and C, respectively. Intracranial progression-free survival was not reached, 2.5 months, and 2.3 months in the 3 cohorts, respectively.
Adverse Events
Treatment-related adverse events of any grade occurred in 97% of cohort A, 68% of cohort B, and 50% of cohort C. Grade 3 or 4 treatment-related adverse events occurred in 54% of cohort A (most common = diarrhea/colitis in 20%, hepatitis in 20%, and rash in 11%), 16% in cohort B (most common = hepatitis in 8%), and 13% in cohort C (most common = headache in 6%). No treatment-related deaths were observed.
The investigators concluded, “Nivolumab combined with ipilimumab and nivolumab monotherapy are active in melanoma brain metastases. A high proportion of patients achieved an intracranial response with the combination. Thus, nivolumab combined with ipilimumab should be considered as a first-line therapy for patients with asymptomatic untreated brain metastases.”
The study was funded by the Melanoma Institute Australia and Bristol-Myers Squibb.
Georgina V. Long, PhD, of Melanoma Institute Australia, University of Sydney, is the corresponding author of The Lancet Oncology article.
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