BACKGROUND: Recent clinical trials have shown that pembrolizumab significantly 
prolonged progression-free survival and overall survival compared with 
ipilimumab in ipilimumab-naïve patients with unresectable or metastatic 
melanoma. However, there has been no published evidence on the 
cost-effectiveness of pembrolizumab for this indication.
OBJECTIVE: To assess the long-term cost-effectiveness of pembrolizumab versus 
ipilimumab in ipilimumab-naïve patients with unresectable or meta-static 
melanoma from a U.S. integrated health system perspective.
METHODS: A partitioned-survival model was developed, which divided overall 
survival time into progression-free survival and postprogression survival. The 
model used Kaplan-Meier estimates of progression-free survival and overall 
survival from a recent randomized phase 3 study (KEYNOTE-006) that compared 
pembrolizumab and ipilimumab. Extrapolation of progression-free survival and 
overall survival beyond the clinical trial was based on parametric functions and 
literature data. The base-case time horizon was 20 years, and costs and health 
outcomes were discounted at a rate of 3% per year. Clinical data-including 
progression-free survival and overall survival data spanning a median follow-up 
time of 15 months, as well as quality of life and adverse event data from the 
ongoing KEYNOTE-006 trial-and cost data from public sources were used to 
populate the model. Costs included those of drug acquisition, treatment 
administration, adverse event management, and disease management of advanced 
melanoma. The incremental cost-effectiveness ratio (ICER) expressed as cost 
difference per quality-adjusted life-year (QALY) gained was the main outcome, 
and a series of sensitivity analyses were performed to test the robustness of 
the results.
RESULTS: In the base case, pembrolizumab was projected to increase the life 
expectancy of U.S. patients with advanced melanoma by 1.14 years, corresponding 
to a gain of 0.79 discounted QALYs over ipilimumab. The model also projected an 
average increase of $63,680 in discounted perpatient costs of treatment with 
pembrolizumab versus ipilimumab. The corresponding ICER was $81,091 per QALY 
($68,712 per life-year) over a 20-year time horizon. With $100,000 per QALY as 
the threshold, when input parameters were varied in deterministic one-way 
sensitivity analyses, the use of pembrolizumab was cost-effective relative to 
ipilimumab in most ranges. Further, in a comprehensive probabilistic sensitivity 
analysis, the ICER was cost-effective in 83% of the simulations.
CONCLUSIONS: Compared with ipilimumab, pembrolizumab had higher expected QALYs 
and was cost-effective for the treatment of patients with unresectable or 
metastatic melanoma from a U.S. integrated health system perspective.
DISCLOSURES: This study was supported by funding from Merck & Co., which 
reviewed and approved the manuscript before journal submission. Wang, 
Pellissier, Xu, Stevinson, and Liu are employees of, and own stock in, Merck & 
Co. Chmielowski has served as a paid consultant for Merck & Co. and received a 
consultant fee for clinical input in connection with this study. Chmielowski 
also reports receiving advisory board and speaker bureau fees from multiple 
major pharmaceutical companies. Wang led the modeling and writing of the 
manuscript. Chmielowski, Xu, Stevinson, and Pellissier contributed substantially 
to the modeling design and methodology. Liu led the data collection work and 
contributed substantially to writing the manuscript. In conducting the analysis 
and writing the manuscript, the authors followed Merck publication polices and 
the "cost-effectiveness analysis alongside clinical trials-good research 
practices and the CHEERS reporting format as recommended by the International 
Society for Pharmacoeconomics and Outcomes Research.