OBJECTIVES::  To estimate and compare the association of cobimetinib + vemurafenib (COBI-VEM) versus other therapeutic options for the first line treatment of metastatic melanoma with BRAF V600 mutation in number needed to treat (NNT) and cost of preventing an event (COPE). METHODS::  NNT was calculated as the inverse of the absolute risk from an intervention in a definite time point (12 months). COPE consisted of the product of total cost of treatment multiplied by the NNT. The studied perspective was the Brazilian Supplementary Health System. The comparators were vemurafenib monotherapy, dabrafenib, nivolumab and ipilimumab. Clinical outcomes were obtained from the main clinical studies considering progression free survival (PFS) curves (CoBRIM, BRIM-3, BREAK-3 and Checkmate67). Treatment cost was based on drug acquisition and adverse events cost. Drug acquisition cost was calculated including drug prices obtained from the official price list published by the Brazilian Ministry of Health and drug dosage from each respective label. Adverse events cost was based on micro-costing, which resource use was defined by specialists and costs were attributed accordingly. The incidence of adverse events were obtained from the pivotal studies. The time horizon considered was 12 months. RESULTS:: The results in 12 months demonstrated the following NNT values: COBI-VEM = 1.92; vemurafenib = 3.33; dabrafenibe = 4.67; nivolumabe = 4.39; ipilimumab = 7.84. In terms of COPE, the COBI-VEM association showed the lowest COPE values when compared to the other therapies (COBI-VEM = BRL 1’136’308; vemurafenib = BRL 1’295’974; dabrafenib = BRL 1’678’091; nivolumab = BRL 1’650’868 and ipilimumab = BRL 2’076’855). CONCLUSIONS:: COBI-VEM demonstrated lower NNT and COPE results, showing that cobimetinib associated to vemurafenib can promote resource savings in terms of COPE when compared to other therapeutic options in the first line treatment of metastatic melanoma with BRAF V600 mutation.