Cost-Effectiveness of Dabrafenib Plus Trametinib Versus Standard Chemotherapy in BRAFV600E-Mutant Pediatric Low-Grade Glioma.
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PURPOSE: Dabrafenib in combination with trametinib (Dab-Tram) is increasingly regarded as an emerging standard of care for patients with BRAFV600E-mutant pediatric low-grade glioma (PLGG) internationally. Given the high costs of these targeted therapies, we estimated the cost-effectiveness of Dab-Tram versus standard chemotherapy in BRAFV600E-mutant PLGG. METHODS: We constructed a microsimulation model to simulate a cohort of patients with BRAFV600E-mutant PLGG from initiation of first-line systemic therapy to death. Clinical efficacy was extrapolated from the TADPOLE phase II clinical trial (ClinicalTrials.gov identifier: NCT02684058). Utilities and long-term risks of late effects were sourced from published literature. Costs were extracted from Canadian data sources. Cost-effectiveness was calculated from a Canadian public health care payer perspective at a discount rate of 1.5%, expressed in 2024 Canadian dollars. The base case modeled lifetime Dab-Tram treatment, to reflect clinical paradigms of indefinite Dab-Tram therapy. Sensitivity analyses exploring minimum treatment durations, price of Dab-Tram, discount rate, use of radiation, and incorporating real-world data were conducted. RESULTS: Dab-Tram was associated with a 2.21 quality-adjusted life-year (QALY) gain at an incremental cost of $554,769 Canadian dollars (CAD) compared with standard chemotherapy. The base case incremental cost-effectiveness ratio (ICER) was $251,027 CAD/QALY. Two-year Dab-Tram resulted in an ICER of $44,740 CAD/QALY, while ICERs across other scenarios ranged from $26,013 CAD to $410,196 CAD/QALY. Results were sensitive to assumed survival distributions and use of independent assessment of TADPOLE outcomes. CONCLUSION: Our findings demonstrate that the cost-effectiveness of Dab-Tram is sensitive to price and duration of treatment, with uncertainty related to clinical effectiveness over the life course and optimal treatment duration. In the context of clinical paradigms favoring indefinite treatment, Dab-Tram is unlikely to prove cost-effective at the present price and would require a price reduction to facilitate sustained access.