Background
Phase III RCT of 118 patients with at least one angiomyolipoma ≥3 cm in the setting of tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.
Interventions and follow up
Arm A: Everolimus 10mg PO daily
Arm B: Placebo
Primary endpoint: angiomyolipoma response rate (≥50% volume reduction)
Arm B: Placebo
Primary endpoint: angiomyolipoma response rate (≥50% volume reduction)
Results
Angiomyolipoma response rate (A vs B): 42% vs 0%, P<.0001
Skin lesion response: favored everolimus
Skin lesion response: favored everolimus
Adverse events
Mucocutaneous (A vs B): stomatitis 48% vs 8%, acne-like lesions 22% vs 5%
Infectious/other (A vs B): nasopharyngitis 24% vs 31%
Infectious/other (A vs B): nasopharyngitis 24% vs 31%
Conclusions
Everolimus produced significant angiomyolipoma volume reduction versus placebo in tuberous sclerosis complex or lymphangioleiomyomatosis-associated disease.
Key Limitations
Surrogate radiographic endpoint rather than renal function or hard clinical outcomes; benign tumor biology distinct from RCC; continued therapy generally required to maintain response; relatively short randomized follow-up.
Clinical Context
Supported FDA approval of everolimus (2012) for renal angiomyolipoma associated with tuberous sclerosis complex not requiring immediate surgery; EMA approval followed. This is a benign-tumor indication distinct from advanced RCC therapy.