Résistance acquise au dabrafenib + trametinib dans l'ATC mutant BRAF (BRAF secondaire / MEK /...

Vue déterministe de l'entité source de la LJAM. L'autorité clinique demeure avec les ID de la source cités et l'état d'approbation de l ́examinateur.

ID	`RF-THYROID-ANAPLASTIC-TRANSFORMATION-PROGRESSION`
Type	Signal d’alerte
État	reviewed 2026-04-27 \| pending_clinical_signoff
Maladies	`DIS-THYROID-ANAPLASTIC`
Sources	`SRC-ATA-THYROID-2015` `SRC-NCCN-THYROID-2025`

Origine du drapeau rouge

Définition	Acquired resistance to dabrafenib + trametinib in BRAF-mutant ATC (secondary BRAF / MEK / RAS / MAPK reactivation, NRAS or KRAS mutations, BRAF amplification), rapid local progression on cytotoxic CRT, new distant metastases (lung, bone, brain), or transformation from differentiated thyroid cancer (DTC) into ATC component (dedifferentiation event) — triggers re-staging, re-biopsy, salvage immunotherapy (pembrolizumab or pembrolizumab + lenvatinib) or trial enrollment.
Direction clinique	en attente
Catégorie	transformation-progression

Logique de déclenchement

{
  "any_of": [
    {
      "finding": "braf_mek_resistance_mutation",
      "value": true
    },
    {
      "finding": "rapid_progression_on_crt",
      "value": true
    },
    {
      "finding": "new_metastatic_disease",
      "value": true
    },
    {
      "finding": "dtc_to_atc_dedifferentiation",
      "value": true
    }
  ],
  "type": "composite_clinical"
}

Notes

Most BRAF+ ATC will progress on dabrafenib + trametinib within 6-12 months due to MAPK pathway reactivation (acquired NRAS / KRAS, BRAF amplification, MEK1 mutation). Salvage options: pembrolizumab monotherapy (KEYNOTE-158 ATC cohort ORR ~16%, durable in responders), pembrolizumab + lenvatinib (ATLAS investigational), or salvage cytotoxic (cisplatin-paclitaxel). DTC→ATC dedifferentiation: ~5-15% of long- standing PTC develops anaplastic transformation — re-biopsy any new rapidly enlarging mass in DTC patient. Brain metastases: stereotactic RT + dabrafenib (CNS-penetrant). Priority 30 reflects critical-tier override given disease tempo.

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