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Intermittent vorinostat in BRAFinhibitor resistant melanoma patients : a headroom analysis

Veijer, C. (2019) Intermittent vorinostat in BRAFinhibitor resistant melanoma patients : a headroom analysis.

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Abstract:Abstract Background: Half of BRAF V600 mutated advanced stage melanoma patients treated with BRAF-MEK inhibition develop drug-resistance with around 12 months. A short treatment with vorinostat for two weeks would eliminate the majority of resistant cells, after which BRAF-MEK inhibition is resumed. This treatment cycle can be repeated over time. The novel therapeutic strategy is currently under investigation in a phase I/II study. To analyze the chance of cost-effectiveness in an early stage, a headroom analysis was performed. Methods: A Markov decision model, consisting of three mutually exclusive health states (on treatment, end-of-life care and death) were modelled to estimate the expected costs and outcomes (quality-adjusted life years; QALYs) for the vorinostat strategy versus the Standard of Care (SoC). For the base case of the vorinostat strategy, a treatment cycle time of 3 months was chosen, with a minimum (+3 months) and maximum (+12 months) expected additional survival to the median overall survival (OS) of the SoC. The sensitivity of the base case to the survival, the additional costs of vorinostat, the incremental quality of life, and the treatment cycle length were analyzed to inform further research prioritization. Results: A treatment cycle of 3 months, combined with the base case costs of vorinostat and a minimum additional survival, resulted in an ICER of € 20,588/QALY. A maximum additional survival would yield an ICER of € 72,507/QALY. Additional costs of vorinostat could rise to € 4,635 in the minimum and to € 2,465 in the maximum extended survival scenario. A shorter treatment cycle increased the chance of cost-effectiveness. Conclusions: The results of this very early cost-effectiveness study suggest that the addition of vorinostat may become a cost-effective intervention. The outcome is counter-intuitive though, since an increasing additional survival in the less expensive vorinostat strategy decreases the chance of cost-effectiveness. Further research should focus on the clinical effects of vorinostat, the feasibility to detect resistance in an early phase, and the survival and quality of life of the SoC.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:44 medicine
Programme:Health Sciences MSc (66851)
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