Everolimus safety and efficacy for renal angiomyolipomas associated with tuberous sclerosis complex: a Spanish expanded access trial.

Background: Renal angiomyolipomas (AML) are usual manifestations of tuberous sclerosis complex (TSC) that may cause aneurism-related haemorrhages and renal impairment. Everolimus has emerged as an alternative to surgery/ embolization. We provide further insight into everolimus safety and efficacy for TSC-related AML. Methods: This was a Spanish expanded access trial including patients aged =18 years with TSC-related AML. They received 10 mg everolimus once daily until AML progression, unacceptable toxicity, death/withdrawal, commercialisation for TSC-related AML, or 1 year after first patient enrolment. The primary outcome was dose-limiting safety according to grade 3/4 adverse events, serious adverse events, or adverse events leading to treatment modification. Secondary outcomes included overall safety and efficacy. Results: Nineteen patients were enrolled and received everolimus for a median of 6.6 (5.3-10.9) months. Eleven (57.9%) remained on 10 mg/day throughout the study and eight (42.1%) required treatment modifications due to adverse events; none permanently discontinued treatment. Adverse events were overall grade 1/2 and most frequently included aphthous stomatitis/mucosal inflammation, hypercholesterolaemia/hypertriglyceridaemia, urinary tract infection, hypertension, dermatitis acneiform, and insomnia. Four (21.1%) patients experienced grade 3 adverse events, none was grade 4, and only one (5.3%) was serious (pneumonia). AML volume was reduced ≥30% in 11 (57.9%) patients and ≥50% in 9 (47.4%); none progressed. Right and left kidney sizes decreased in 16 and 14 patients, respectively. Conclusions: These findings support the benefit of everolimus for renal AML due to a manageable safety profile accompanied by reduced AML and kidney volumes. [ABSTRACT FROM AUTHOR]