Everolimus (mTOR inhibitor) is FDA-approved (2012) for renal angiomyolipoma (AML) associa...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-TSC1-TSC-RENAL-AML |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-LAM |
| Sources | SRC-NCCN-KIDNEY-2025 |
Actionability Facts
| Biomarker | BIO-TSC1 |
|---|---|
| Variant | TSC1 or TSC2 germline loss-of-function — Tuberous Sclerosis Complex with renal angiomyolipoma (AML) ≥3 cm or growing, at risk for hemorrhage (Wunderlich syndrome) |
| Disease | DIS-LAM |
| ESCAT tier | IB |
| Recommended combinations | everolimus 10 mg PO QD (TSC renal AML ≥3 cm growing/at risk; EXIST-2 regimen; monitor trough levels target 3–15 ng/mL) |
| Evidence summary | Everolimus (mTOR inhibitor) is FDA-approved (2012) for renal angiomyolipoma (AML) associated with TSC. EXIST-2 phase III (Bissler et al., Lancet 2013): N=118 (everolimus 10 mg vs placebo); primary endpoint: AML response rate (≥50% reduction in sum of longest diameters of target AMLs). AML response: 42% (everolimus) vs 0% (placebo) (p<0.0001); mDOR: not reached. Disease stabilization: 96% vs 55%. Everolimus also reduces AML growth rate and risk of spontaneous hemorrhage (Wunderlich syndrome). In TSC patients with AMLs ≥3 cm, prophylactic everolimus is preferred to prophylactic embolization per current guidelines. Note: TSC1 germline is the biomarker for eligibility (Tuberous Sclerosis Complex diagnosis required); sporadic renal AML without TSC features are a different entity. ESCAT IB: phase III RCT data but for renal angiomyolipoma (benign disease context, not malignant RCC — thus IB not IA despite strong evidence). |
Notes
ESCAT IB (note: disease_id is DIS-RCC as closest match; this indication is specifically renal angiomyolipoma in TSC — a benign smooth-muscle/fat tumor, not RCC). TSC management requires multidisciplinary approach (neurology, nephrology, pulmonology/LAM, dermatology, ophthalmology, genetics). Renal AML surveillance: MRI or ultrasound q1–3 years depending on size and growth; embolization reserved for acute hemorrhage (Wunderlich syndrome) or when surgery required. Everolimus vs embolization: everolimus preferred for growing AML <3 cm or multiple AMLs; embolization for acute hemorrhage or very large (>8 cm) AMLs. Sorafenib, sunitinib, and mTOR inhibitors (everolimus, temsirolimus) are approved for conventional clear-cell RCC — different indication from TSC-associated AML. Malignant transformation of renal AML is extremely rare (<1%).
Used By
No reverse references found in the YAML corpus.