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.


BACKGROUND
EudraCT number 2012-005397-63 ; date of registration 22 Nov 2012.
Department of Nephrology, Hospital Universitario Infanta Cristina, REDINREN, Avenida de Elvas, S/N, 06006, Badajoz, Spain.
Nicolás Roberto
NR
Robles
Department of Nephrology, Hospital Universitario La Paz, REDINREN, Paseo de la Castellana, 261, 28046, Madrid, Spain.
Ramón
R
Peces
Department of Urology, Instituto Valenciano de Oncología, Calle del Profesor Beltrán Bàguena, 8, 46009, Valencia, Spain.
Álvaro
Á
Gómez-Ferrer
Department of Urology, Hospital Universitario 12 de Octubre, Avenida de Córdoba, S/N, 28041, Madrid, Spain.
Felipe
F
Villacampa
Department of Urology, Hospital Universitario Puerta del Mar, Avenida Ana Viya, 21, 11009, Cádiz, Spain.
Jose Luis
JL
Álvarez-Ossorio
Department of Oncology, Hospital Universitario Clínico San Carlos, Calle del Profesor Martín Lagos, S/N, 28040, Madrid, Spain.
Pedro
P
Pérez-Segura
Department of Urology, Hospital Universitario Vall d'Hebron, Paseo de la Vall d'Hebron, 119-129, 08035, Barcelona, Spain.
Juan
J
Morote
Department of Urology, Hospital Universitario Virgen de la Victoria, Campus de Teatinos, S/N, 29010, Málaga, Spain.
Bernardo
B
Herrera-Imbroda
Department of Nephrology, Hospital General Universitario de Ciudad Real, Calle del Obispo Rafael Torija, S/N, 13005, Ciudad Real, Spain.
Javier
J
Nieto
Department of Urology, Hospital Universitario Puerta de Hierro Majadahonda, Calle de Manuel de Falla, 1, 28222, Majadahonda, Spain.
Joaquín
J
Carballido
Department of Oncology, Hospital Clínico Universitario de Santiago de Compostela, Travesía de Choupana, S/N, 15706, Santiago de Compostela, Spain.
Urbano
U
Anido
Department of Medical Affairs, Novartis Farmacéutica S.A, Gran Via de les Corts Catalanes, 764, 08013, Barcelona, Spain.
Marian
M
Valero
Department of Medical Affairs, Novartis Farmacéutica S.A, Gran Via de les Corts Catalanes, 764, 08013, Barcelona, Spain.
Cristina
C
Meseguer
Inherited Renal Diseases, Department of Nephrology, Fundació Puigvert, REDINREN, IIB Sant Pau, Universitat Autónoma de Barcelona, Cartagena, 340-350, 08025, Barcelona, Spain. rtorra@fundacio-puigvert.es.
Roser
R
Torra
Angiomyolipoma; Everolimus; Safety; Tuberous sclerosis complex
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