BRAF V600E in anaplastic thyroid carcinoma (ATC, ~25-50% of cases): dabrafenib + trametin...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-BRAF-V600E-THYROID-ANAPLASTIC |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-THYROID-ANAPLASTIC |
| Sources | SRC-CIVIC SRC-NCCN-THYROID-2025 |
Actionability Facts
| Biomarker | BIO-BRAF-V600E |
|---|---|
| Variant | V600E (exon 15, kinase domain — present in ~25-50% of anaplastic thyroid carcinoma) |
| Disease | DIS-THYROID-ANAPLASTIC |
| ESCAT tier | IA |
| Recommended combinations | 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) |
| Evidence summary | 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. |
Notes
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.
Used By
No reverse references found in the YAML corpus.