OBJECTIVES: To assess the cost-effectiveness of pembrolizumab to treat unresectable or metastatic melanoma in patients progressing after treatment with ipilimumab, and if BRAF^v600positive mutation, a BRAF inhibitor. The relevant comparator is English best supportive care (BSC), including dacarbazine. METHODS: A three-state partitioned survival model was developed to estimate the cost-effectiveness of pembrolizumab compared with BSC over a 30 year time horizon. Efficacy and quality of life were derived from KEYNOTE-002, a phase II clinical trial comparing pembrolizumab to investigators choice of chemotherapy. Since overall survival (OS) data were affected by a high degree of crossover, various statistical models were used to adjust for crossover with the 2-stage adjustment, using progression as a secondary baseline, found to be the most appropriate. Pembrolizumab OS was extrapolated using long-term ipilimumab data, supported by results of the KEYNOTE-002 clinical trial, and melanoma clinical experts’ feedback on commonality of expected long-term survival profile. Quality of life was based on time to death health states using KEYNOTE-002 EQ-5D data. Adverse events were incorporated based upon KEYNOTE-002 data which showed a favourable safety profile when compared to chemotherapy, with grade 3-5 adverse events numerically higher in the chemotherapy control arm. RESULTS: Pembrolizumab was predicted to increase the life expectancy of patients by 1.59 years, which corresponds to a gain of 1.19 QALYS. In the base case analysis, the ICER is £42,923 (confidential discount included). These results are sensitive to curve fit parameters for progression-free survival and the hazard-ratio for overall survival estimated from the cross-over adjustment and a robust to changes in value parameters and assumptions in the cost-effectiveness analysis. CONCLUSIONS: As an end of life therapy for English patients with advanced melanoma previously treated with ipilimumab, pembrolizumab is a cost-effective therapeutic option when compared to best supportive care (including conventional chemotherapy).