(ChemotherapyAdvisor) – Ipilimumab has activity in some patients with advanced melanoma and brain metastases — particularly when metastases are small and asymptomatic — with no unexpected toxic effects, investigators concluded in the Lancet Oncology online March 26.
“As far as we are aware, our prospective study was the first to investigate ipilimumab specifically in patients with advanced melanoma and brain metastases,” the investigators wrote. The multicenter, open-label, Phase 2 trial enrolled 72 patients with brain metastases in two parallel cohorts between July 2008 and June 2009. Those in cohort A were neurologically asymptomatic and not receiving corticosteroid treatment at study entry (n=51); those in cohort B were symptomatic and on a stable dose of corticosteroids (n=21).
Patients received one dose of ipilimumab 10mg/kg IV every three weeks to a total of four doses. Those clinically stable at 24 weeks were eligible to continue treatment with ipilimumab 10mg/kg IV every 12 weeks.
After 12 weeks, 9 patients in cohort A (18%) and 1 patient in cohort 1 (5%) exhibited disease control, the primary end point, defined as complete response, partial response, or stable disease after 12 weeks. When the brain alone was assessed, 12 patients in cohort A (24%) and 2 in cohort B (10%) achieved disease control, the investigators found. Disease control outside the brain was noted in 14 patients (27%) in cohort A and in 1 (5%) in cohort B.
The most common grade 3 adverse events (AEs) in cohort A were diarrhea (12%) and fatigue (12%); in cohort B, they were dehydration (10%), hyperglycemia (10%), and increased concentrations of serum aspartate aminotransferase (10%). One patient in each cohort had grade 4 confusion. One patient in cohort A died of drug-related complications of immune-related colitis. No excessive or unique CNS toxicities as a result of ipilimumab given to patients with brain metastases were observed.
An accompanying comment notes that “ipilimumab is now a standard of care for advanced melanoma and, in our view, these data show that the presence of brain metastases should not prevent the use of ipilimumab.”