(005) Cost-Effectiveness of Neoadjuvant Dabrafenib, Trametinib, and Pembrolizumab for BRAF V600E-Mutated Anaplastic Thyroid Carcinoma

Introduction: BRAF V600E–mutated anaplastic thyroid cancer (ATC) is aggressive, and neoadjuvant targeted and immune-based therapies have shown promise in treatment. This study evaluates whether neoadjuvant triplet therapy provides superior cost-effectiveness compared to dual targeted therapy in this population.

Methods: A partitioned survival model compared DTP to historical standard of care (doxorubicin/cisplatin plus hyperfractionated radiation). Clinical inputs derived from Zafereo et al. (ASCO 2025; n=36) and published literature. Costs (2025 USD) included drugs, surgery, radiation, and palliative care. Outcomes measured as quality-adjusted life-years (QALYs). Probabilistic sensitivity analysis (PSA; 10,000 iterations) assessed uncertainty. A secondary analysis compared DTP to dabrafenib-trametinib alone.

Results: DTP achieved median overall survival of 21 months versus 6 months with historical treatment. Total costs were $462,143 (DTP) versus $184,114 (historical), yielding 1.54 versus 0.27 QALYs. The incremental cost-effectiveness ratio (ICER) was $218,965/QALY. PSA showed a median ICER of $329,016/QALY (95% CI: $182,864-$549,182). Probability of cost-effectiveness was 5% at $200,000/QALY and 38% at $300,000/QALY. Compared to dabrafenib-trametinib alone (ROAR trial; median OS 14.5 months), the ICER was $180,414/QALY with 50% probability of cost-effectiveness at $200,000/QALY.

Conclusions: Neoadjuvant DTP for BRAF V600E-mutated ATC exceeds conventional cost-effectiveness thresholds but delivers substantial survival benefit (15-month gain) in a uniformly fatal disease. Higher willingness-to-pay thresholds for rare cancers may support coverage. Drug pricing negotiations could improve value.