Effectiveness and cost-effectiveness of combination therapy versus monotherapy in malignant melanoma

BACKGROUND: Until 2010, stage III or IV malignant melanoma (MM) had a poor prognosis. The discovery of immune checkpoint inhibitors (ICIs) in 2011 changed the treatment landscape. Promising results in patient survival with a checkpoint inhibitor prompted research into combination therapies. In 2016, the first combination therapy has been approved as first-line therapy for advanced MM. OBJECTIVE: The aim of this work is to investigate to what extent combination therapy is (cost-)effective compared to monotherapy in stage III or IV MM. METHODS: A systematic literature search was performed (Web of Science, PubMed, PubPharm, EconLit, and Cochrane Library); searching for publications published over the past decade that examine the cost-effectiveness in terms of cost/QALY and the effectiveness in terms of survival and response of combination therapy in comparison to monotherapy in stage III or IV MM patients. RESULTS: A total of 11 randomized controlled trials (RCTs) and five cost–utility analyses met our inclusion criteria. Nine clinical trials demonstrated superiority of combination therapy over monotherapy. The combination of B-rapidly accelerated fibrosarcoma (BRAF) protein and mitogen-activated kinase (MEK) protein inhibitors is not cost-effective in any country. Three analyses demonstrate the cost-effectiveness of combination therapy with ICI compared to monotherapy. CONCLUSION: Combination therapy is more effective compared to monotherapy. While combined ICIs are cost-effective compared to monotherapy, this is not the case for the combination of BRAF and MEK inhibitors.