BRAF V600E em carcinoma da tireoide anaplásico (ATC, ~25-50% dos casos): dabrafenib + trametina...
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| ID | BMA-BRAF-V600E-THYROID-ANAPLASTIC |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-THYROID-ANAPLASTIC |
| Fontes | SRC-CIVIC SRC-NCCN-THYROID-2025 |
Fatos de ação
| Biomarcador | BIO-BRAF-V600E |
|---|---|
| Variante | V600E (exon 15, domínio da quinase — presente em ~25-50% de carcinoma da tireóide anaplásico) |
| Doença | DIS-THYROID-ANAPLASTIC |
| Nível ESCAT | IA |
| Combinações recomendadas | dabrafenib + trametinib (1L V600E ATC per SRC-NCCN-THYROID-2025), neoadjuvant dabrafenib + trametinib → surgery → adjuvant systemic ± RT (initially unresectable, per SRC-NCCN-THYROID-2025) |
| Contraindicated monotherapy | BRAF inhibitor monotherapy (paradoxical MAPK activation; combination with MEK inhibitor required per SRC-NCCN-THYROID-2025) |
| Resumo das provas | BRAF V600E in anaplastic thyroid carcinoma (ATC, ~25-50% of cases): dabrafenib + trametinib has tumor-agnostic FDA approval for BRAF V600E unresectable/metastatic disease and is preferred 1L for V600E-mutant ATC per SRC-NCCN-THYROID-2025. The pivotal ROAR basket trial (Subbiah JCO 2018 — ATC cohort ORR 69%, mOS ~14 mo, dramatic response in a historically rapid-fatal disease — historical mOS ~5 mo) drove the 2018 FDA accelerated approval (full conversion 2022 with pan-cancer broadening). Consider neoadjuvant dabrafenib+trametinib to enable surgery in initially unresectable V600E ATC per SRC-NCCN-THYROID-2025. |
Notas
ESCAT IA / OncoKB Level 1. ATC is a clinical emergency — initiate BRAF testing on the same day as biopsy diagnosis per SRC-NCCN-THYROID-2025 ("RAID" workflow). Resistance: development of MEK reactivation, alternative MAPK isoforms; triple combination with anti-PD-1 (ATLEP trial) is investigational. Source-gap: SRC-ROAR-SUBBIAH-2018 not yet ingested.
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