Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe.,We interrogated data from UK EAP patients to inform future clinical practice.,Clinicians registered in the UK EAP provided anonymized patient data using a prespecified variable fields datasheet.,Data collected were baseline patient characteristics, treatment delivered, toxicity, response, progression-free survival and overall survival (OS).,Data were received for 193 previously treated metastatic melanoma patients, whose primary sites were cutaneous (82%), uveal (8%), mucosal (2%), acral (3%) or unknown (5%).,At baseline, 88% of patients had a performance status (PS) of 0-1 and 20% had brain metastases.,Of the patients, 53% received all four planned cycles of ipilimumab; the most common reason for stopping early was disease progression, including death from melanoma.,Toxicity was recorded for 171 patients, 30% of whom experienced an adverse event of grade 3 or higher, the most common being diarrhoea (13%) and fatigue (9%).,At a median follow-up of 23 months, the median progression-free survival and OS were 2.8 and 6.1 months, respectively; the 1-year and 2-year OS rates were 31 and 14.8%, respectively.,The 2-year OS was significantly lower for patients with poorer PS (P<0.0001), low albumin concentrations (P<0.0001), the presence of brain metastases (P=0.007) and lactate dehydrogenase levels more than two times the upper limit of normal (P<0.0001) at baseline.,These baseline characteristics are negative predictors of benefit from ipilimumab and should be taken into consideration before prescription.
The immunotherapeutic agent ipilimumab has helped address a significant unmet need in the treatment of advanced melanoma.,Ipilimumab is a fully human monoclonal antibody that targets cytotoxic T-lymphocyte antigen-4 (CTLA-4), thereby augmenting antitumor immune responses.,After decades in which a number of clinical trials were conducted, ipilimumab was the first therapy to improve overall survival in a randomized, controlled phase III trial of patients with advanced melanoma.,These results led to the regulatory approval of ipilimumab at 3 mg/kg for the treatment of unresectable or metastatic melanoma.,More than 17,000 patients worldwide have received ipilimumab, either as a commercial drug at 3 mg/kg or in clinical trials and expanded access programs at different doses.,Consistent with its proposed mechanism of action, the most common toxicities associated with ipilimumab therapy are inflammatory in nature.,These immune-related adverse events were mostly reversible when effective treatment guidelines were followed.,Importantly, long-term follow-up of patients who received ipilimumab in a phase III trial showed that 24% survived at least two years, and in phase II studies, a proportion of patients survived at least five years.,Evaluation of ipilimumab is ongoing in the adjuvant setting for melanoma, and for advanced disease in nonsmall cell lung, small cell lung, prostate, ovarian, and gastric cancers.