FGFR2 fusion or rearrangement in advanced/metastatic intrahepatic cholangiocarcinoma (~10...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-CHOLANGIO-FGFR2-FUSION-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-30 \| pending_clinical_signoff
Diseases	`DIS-CHOLANGIOCARCINOMA`
Sources	`SRC-ESMO-BTC-2023` `SRC-FIGHT-202` `SRC-NCCN-HEPATOBILIARY`

Red Flag Origin

Definition	FGFR2 fusion or rearrangement in advanced/metastatic intrahepatic cholangiocarcinoma (~10–20% of iCCA; rare in extrahepatic / gallbladder). Treatment-defining for 2L+: pemigatinib (FIGHT-202 ORR 35.5%, mPFS 6.9 mo, mOS 21.1 mo; FDA Apr 2020) preferred when FGFR2 fusion confirmed; futibatinib (FOENIX-CCA2) covalent FGFR-TKI alternative, including some pemigatinib-resistance variants. Common partners: BICC1-FGFR2, FGFR2-AHCYL1, FGFR2-CCDC6.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-CHOLANGIO-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "fgfr2_fusion",
      "value": true
    },
    {
      "finding": "fgfr2_rearrangement",
      "value": "positive"
    },
    {
      "finding": "fgfr2_status",
      "value": "fusion_positive"
    }
  ],
  "type": "biomarker"
}

Notes

Detection: RNA-NGS preferred (captures fusion partners); DNA-NGS with fusion-aware caller acceptable; FISH break-apart secondary. Mandatory pre-treatment NGS in advanced iCCA (NCCN cat 1 testing). Class toxicity: hyperphosphatemia (~50%) — phosphate binders + low-phosphate diet; retinal pigment epithelial detachment (serous retinopathy) — baseline + serial ophtho exam; nail / skin / mucosal toxicity; alopecia. Resistance: gatekeeper V564F + molecular-brake mutations; futibatinib retains some activity. UA access: neither pemigatinib nor futibatinib registered — named-patient / EAP only. SRC-FIGHT-202 currently a stub (citation TBD); flagged for source ingestion completion.

Used By

Algorithms

ALGO-CHOLANGIO-2L - ALGO-CHOLANGIO-2L