A cost-effectiveness analysis of trametinib plus dabrafenib as first-line therapy for metastatic BRAF V600-mutated melanoma in the Swiss setting.
BACKGROUND
The treatment of patients with metastatic melanomas that harbour BRAF V600E or V600K mutations with trametinib plus dabrafenib appears to be superior to treatment with vemurafenib alone. This treatment regimen is likely to become available in Switzerland in the near future.


OBJECTIVE
To determine the cost-effectiveness of trametinib plus dabrafenib.


METHODS
A Markov cohort simulation was conducted to model the clinical course of typical patients with metastatic melanoma. Information on response rates, clinical condition and follow-up treatments were derived and transition probabilities estimated based on the results of a clinical trial that compared treatment with trametinib plus dabrafenib vs. vemurafenib alone.


RESULTS
Treatment with trametinib plus dabrafenib was estimated to cost an additional CHF199 647 (Swiss francs) on average and yield a gain of 0·52 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of CHF385 603 per QALY. Probabilistic sensitivity analyses showed that a willingness-to-pay threshold of CHF100 000 per QALY would not be reached at the current US price of trametinib.


CONCLUSIONS
The introduction of trametinib in Switzerland at US market prices for the treatment of metastatic BRAF V600-mutated melanoma with trametinib plus dabrafenib is unlikely to be cost-effective compared with vemurafenib monotherapy. A reduction in the total price of the combination therapy is required to achieve an acceptable cost-effectiveness ratio for this clinically promising treatment.
Institute of Pharmaceutical Medicine (ECPM), University of Basel, Klingelbergstraße 61, Basel, CH-4056, Switzerland.|SAKK Coordinating Centre, Bern, Switzerland.
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Matter-Walstra
Department of Dermatology, University Hospital Zürich, Zürich, Switzerland.
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Braun
SAKK Coordinating Centre, Bern, Switzerland.
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Kolb
Institute of Pharmaceutical Medicine (ECPM), University of Basel, Klingelbergstraße 61, Basel, CH-4056, Switzerland.
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Ademi
Department of Dermatology, University Hospital Zürich, Zürich, Switzerland.
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Dummer
SAKK Coordinating Centre, Bern, Switzerland.|Department of Oncology, University Hospital Zürich, Zürich, Switzerland.
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Pestalozzi
Institute of Pharmaceutical Medicine (ECPM), University of Basel, Klingelbergstraße 61, Basel, CH-4056, Switzerland.|Epidemiology, Biostatistics and Prevention Institute, University of Zürich, Zürich, Switzerland.
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Schwenkglenks
D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004334:Drug Administration Schedule; D016527:Drug Costs; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000191:economics; D008545:Melanoma / Q000188:drug therapy* / Q000191:economics / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D010091:Oximes / Q000008:administration & dosage / Q000191:economics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D011728:Pyridones / Q000008:administration & dosage / Q000191:economics; D011744:Pyrimidinones / Q000008:administration & dosage / Q000191:economics; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000235:genetics; D013557:Switzerland; D016896:Treatment Outcome
D007093:Imidazoles; D010091:Oximes; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib