Enfortumab vedotin (EV) contraindication in urothelial carcinoma — MMAE-related toxicity...

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

ID	`RF-UROTHELIAL-EV-CONTRAINDICATED`
Type	Red flag
Status	reviewed 2026-05-09 \| pending_clinical_signoff
Diseases	`DIS-UROTHELIAL`
Sources	`SRC-EV302-POWLES-2024` `SRC-NCCN-BLADDER-2025`

Red Flag Origin

Definition	Enfortumab vedotin (EV) contraindication in urothelial carcinoma — MMAE-related toxicity exclusions that preclude EV+pembrolizumab (EV-302/KEYNOTE-A39 exclusion criteria): (1) pre-existing severe peripheral neuropathy (Grade ≥2) — MMAE causes additive neuropathy; (2) uncontrolled diabetes mellitus — EV-related hyperglycemia risk; (3) severe corneal disease or active keratopathy — EV-class ocular toxicity. Fires to route EV-ineligible patients to platinum-based chemotherapy + avelumab maintenance.
Clinical direction	de-escalate
Category	fitness-eligibility
Shifts algorithm	ALGO-UROTHELIAL-METASTATIC-1L

Trigger Logic

{
  "any_of": [
    {
      "comparator": ">=",
      "finding": "neuropathy_grade",
      "threshold": 2
    },
    {
      "finding": "diabetic_neuropathy",
      "value": true
    },
    {
      "finding": "skin_disease_severe",
      "value": true
    },
    {
      "finding": "ocular_disease",
      "value": "severe"
    }
  ],
  "type": "eligibility"
}

Notes

EV contraindication composite. Patient fixture ev_pembro_eligible=true, neuropathy_grade=0, diabetic_neuropathy=false, skin_disease_severe=false, ocular_disease="none" → RF does NOT fire → algo step 1 none_of passes → IND-UROTHELIAL-METASTATIC-1L-EV-PEMBRO selected. ocular_disease=="severe" check: fixture has "none" so this is false. Partial — full CTCAE grading and HbA1c checks would improve precision.

Used By

Algorithms

ALGO-UROTHELIAL-METASTATIC-1L - ALGO-UROTHELIAL-METASTATIC-1L