Efficacy and Safety Data from Patients with Advanced Melanoma and Brain Metastases Participating in the European Ipilimumab Expanded Access Programme (eap) in Italy

ABSTRACT Purpose Patients with melanoma brain metastases have a very poor prognosis and are usually excluded from melanoma clinical trials. The EAP provided an opportunity to evaluate the feasibility of ipilimumab treatment in this patient population outside of a controlled clinical trial in Italy. Methods Ipilimumab was available upon physician request for patients aged ≥16 years with unresectable stage III /IV melanoma, including those with asymptomatic brain metastases, who had either failed systemic therapy or were intolerant to ≥1 systemic treatment. Induction therapy with ipilimumab was 3 mg/kg every 3 weeks for 4 doses. Tumour assessments were conducted at baseline and after completion of induction therapy using immune-related response criteria. Patients were monitored for adverse events (AEs), including immune-related AEs, within 3 to 4 days of each ipilimumab dose using Common Terminology Criteria for Adverse Events v.3.0. Results Of 848 patients with advanced melanoma participating in the EAP in Italy, 144 (17%) had asymptomatic brain metastasis. Of these, data are available for 84 patients. With a median follow-up of 3 months, the disease control rate among 74 evaluable patients was 16.2%, comprising four patients with a partial response and eight with stable disease. As of April 2012, median progression-free survival and overall survival among patients with brain metastases were 2.5 months and 3.8 months, respectively. In total, 50.0% patients reported an AE of any grade, most of which were drug-related (40.5%). Grade 3/4 AEs were reported by 28.5% patients and considered drug-related in 15.5%. The most common grade 3/4 drug-related adverse events were diarrhoea (n = 3; 3.6%) and liver dysfunction (n = 3; 3.6%). AEs were generally reversible with treatment as per protocol-specific guidelines. Conclusions Ipilimumab shows activity in patients with advanced melanoma metastatic to brain, with safety results consistent to what has been previously reported for ipilimumab. Disclosure P. Queirolo: Paola Queirolo has acted as an advisor for Roche, GlaxoSmithKline, Bristol-Myers Squibb and Schering-Plough and received honoraria from Bristol-Myers Squibb and Roche. E. Simeone: Ester Simeone has received honoraria from Bristol-Myers Squibb. All other authors have declared no conflicts of interest.