In our open-label, single-arm phase 2 trial, we enrolled patients 18 years or older with measurable, locally advanced, unresectable stage III or stage IV melanoma between July 6, 2010, and April 14, 2011. Eligible patients had a life expectancy of 16 weeks or more and an Eastern Cooperative Oncology Group performance status of 1 or less, and could have received a maximum of one previous line of chemotherapy. Participants received induction treatment of 10 mg/kg intravenous ipilimumab every 3 weeks to a total of four doses, and 100 mg/m2 intravenous fotemustine weekly for 3 weeks and then every 3 weeks from week 9 to week 24. Patients with a confirmed clinical response were eligible for maintenance treatment from week 24, with ipilimumab every 12 weeks and fotemustine every 3 weeks. The primary endpoint was the proportion of patients with immune-related disease control as established with immune-related response criteria. Analyses were done per protocol. This trial is registered with EudraCT, number 2010-019356-50, and with , number .
86 patients were eligible for treatment, of whom 20 had asymptomatic brain metastases at baseline. 40 patients in the study population achieved disease control (46¡¤5 % , 95 % CI 35¡¤7-57¡¤6), as did ten with brain metastases (50¡¤0 % , 27¡¤2-72¡¤8). 47 patients (55 % ) had grade 3 or 4 treatment-related adverse events, of which the most common was myelotoxicity (thrombocytopenia in 21 [24 % ] patients and neutropenia in 16 [19 % ]). The most common grade 3 or 4 immune-related adverse events were hepatic: 21 patients (24 % ) had grade 3 or 4 increases in concentrations of alanine aminotransferase or aspartate aminotransferase.
The combination of ipilimumab plus fotemustine has clinical activity in patients with metastatic melanoma, including those with brain metastases.
Bristol-Myers Squibb.