OBJECTIVES : To evaluate the cost-effectiveness of dabrafenib in combination with trametinib in comparison to pembrolizumab in the adjuvant setting of stage III high-risk BRAF V600E positive melanoma after surgical resection from the perspective of the Brazilian Private Healthcare System (BPHS).

METHODS : A non-homogeneous, semi-Markov model was developed to simulate costs and outcomes at six-month cycles over lifetime horizon. Patients entered the model in the recurrence-free survival (RFS) state and moved to other 4 states based on recurrence, which may be (1)locoregional or distant [(2)first-line and (3)second-line distant recurrences], and (4)death (representing the absorptive state). The transition probabilities from dabrafenib+trametinib were based on data from the COMBI-AD study and the effects of pembrolizumab were modelled based on RFS hazard ratios (HR) from a network meta-analysis that used watch and wait as a common comparator (HR:0.57; CI 95%:0.43-0.75). Parametric survival distributions were defined based on main statistics criteria, also including clinical plausibility. The effectiveness outcomes were measured in life years (LYs) and quality-adjusted life years (QALYs). The costs included BRAF testing, drugs acquisition, drug administration, disease monitoring, subsequent metastatic-treatment lines, surgery, end-of-life care and the management of adverse events. Half-cycle corrections and 5% discount rate were applied. Uncertainty of the parameters and robustness of the results were evaluated using deterministic and probabilistic sensitivity analyses.

RESULTS : Combination of dabrafenib+trametinib was dominant versus pembrolizumab, with a cost saving of 1,912 dollars (1USD=3.97BRL/May/2019) and a gain of 0.18 QALYs and 0.20 LYs. The results of the sensitivity analyses showed robustness of the model, with the main uncertain parameters represented by relative dose intensity and medication costs.

CONCLUSIONS : From the BPHS perspective, dabrafenib+trametinibe is a cost-saving alternative when compared to pembrolizumab for the adjuvant treatment of stage III high-risk BRAF V600E-positive melanoma after surgical resection, which shows that targeted therapy is a more efficient treatment than immunotherapy.