Baseline organ dysfunction precluding standard imatinib / sunitinib / regorafenib / avapr...

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

ID	`RF-GIST-ORGAN-DYSFUNCTION`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-GIST`
Sources	`SRC-ESMO-SARCOMA-2024` `SRC-NCCN-GIST-2025`

Red Flag Origin

Definition	Baseline organ dysfunction precluding standard imatinib / sunitinib / regorafenib / avapritinib in GIST: LVEF <50% (sunitinib + regorafenib cardiotoxicity, hypertension), CrCl <30 mL/min (TKI-class dose adjustment, especially regorafenib), bilirubin >3× ULN (imatinib / avapritinib hepatic clearance — dose-limiting toxicity), or uncontrolled hypertension (sunitinib / regorafenib contraindicated).
Clinical direction	de-escalate
Category	organ-dysfunction

Trigger Logic

{
  "any_of": [
    {
      "comparator": "<",
      "finding": "lvef_percent",
      "threshold": 50
    },
    {
      "comparator": "<",
      "finding": "creatinine_clearance_ml_min",
      "threshold": 30
    },
    {
      "comparator": ">=",
      "finding": "bilirubin_ratio_to_uln",
      "threshold": 3
    },
    {
      "finding": "uncontrolled_hypertension",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Imatinib well-tolerated in mild-moderate hepatic impairment; severe hepatic dysfunction (Child-Pugh C) requires dose reduction. Sunitinib (2L) — significant cardiac signal: LVEF decline, hypertension, hand-foot syndrome — require baseline ECHO + serial monitoring, hold if LVEF drops >15% or below 50%. Regorafenib (3L) — hepatotoxicity (FDA boxed warning), severe hand-foot, hypertension — contraindicated if Child-Pugh C. Avapritinib carries CNS bleeding signal; QTc monitoring not required but cognitive effects observed at 300 mg. Uncontrolled hypertension is gating for sunitinib/regorafenib — optimize before initiation.

Used By

Indications

IND-GIST-4L-RIPRETINIB - IND-GIST-4L-RIPRETINIB