OBJECTIVES

To assess the cost-effectiveness of BRAF-targeted agents for the treatment of BRAFV600 mutation positive unresectable or metastatic (advanced) melanoma (AM) in the Irish healthcare setting.

METHODS

The cost-effectiveness analysis was conducted with reference to the Guidelines for Economic Evaluation in Ireland. The included interventions were all treatments licensed specifically for BRAFV600 mutation positive AM (vemurafenib, dabrafenib, trametinib, cobimetinib). The comparator was intravenous dacarbazine. A de-novo three-health state partitioned survival model was constructed. The perspective was that of the Irish health service, with a cycle length of one week and time horizon of 30 years. A discount rate of 5% was applied to costs and outcomes.

Efficacy inputs were derived through systematic review, and Bayesian Network meta-analysis. Kaplan-Meier curves were digitised and recreated using R version 3.5.0 to provide baseline estimates of hazard. Parametric methods were used to extrapolate survival, with external data from outcome registries used to inform long-term projections. EQ-5D-3L utility data from the pivotal trials were applied. Resource use estimates were derived from the literature and analysis of national hospital episode statistics. Diagnosis-related group costs were used (€ 2018), supplemented with cost data from Irish tertiary hospitals and the literature. A full incremental analysis was conducted, with incremental cost per quality adjusted life year (QALY) as the outcome. Probabilistic and deterministic sensitivity analyses were conducted.

RESULTS

Vemurafenib and vemurafenib in combination with cobimetinib were excluded by extended dominance, and dabrafenib was dominated by dabrafenib in combination with trametinib, for which the incremental cost-effectiveness ratio versus dacarbazine was €349,233/QALY (incremental costs €436,946, incremental QALYs 1.24). Outcomes were most sensitive to assumptions regarding survival, treatment costs, and discount rates. The probability of cost-effectiveness at the Irish cost-effectiveness threshold of €45,000 is 0%.

CONCLUSIONS

Targeted treatments for BRAF V600 mutation positive AM are not cost effective at the Irish cost-effectiveness threshold of €45,000/QALY.