Cost-effectiveness of treatment sequences for BRAF-mutant advanced melanoma in the Netherlands using a health economic model

Background: This study aims to evaluate the cost-effectiveness of treatment sequences for patients with advanced melanoma with a BRAF mutation in the Netherlands from a societal perspective. Methods: A semi-Markov model with a life-time horizon has been used to evaluate cost-effectiveness of 21 treatment sequences. Real-world data from the Dutch Melanoma Treatment Registry (DMTR) were used to estimate time to progression, next treatment and death. Utilities by health state as well as hospital costs, health care costs outside the hospital, patient and family costs and productivity costs were also derived from the DMTR. Drug costs were estimated based on the recommended dose and duration of treatment. Incremental costeffectiveness ratios (ICERs) were presented as incremental costs per QALY gained. Results: Health benefits of treatment sequences consisting of targeted therapies and immunotherapies vary between 2.3 and 5.8 QALYs gained per patient when compared to chemotherapy. The increase in costs varies between <euro>112,000 and <euro>383,000. The efficiency frontier consists of nivolumab in the first line followed by ipilimumab in the second line (ICERs of <euro>42,000/QALY and <euro>44,000/QALY), nivolumab in the first line followed by encorafenib plus binimetinib in the second line (ICERs of <euro>71,000/QALY and <euro>68,000/QALY) and nivolumab plus ipilimumab in the first line followed by encorafenib plus binimetinib in the second line (ICERs of <euro>74,000/ QALY and <euro>76,000/QALY). The first treatment given within a sequence as well as assumptions regarding treatment duration have a substantial impact on cost-effectiveness outcomes. Conclusion: The ICERs can be considered cost-effective at different cost-effectiveness thresholds.