Dataset Information

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

ABSTRACT: 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.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.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.These findings support the benefit of everolimus for renal AML due to a manageable safety profile accompanied by reduced AML and kidney volumes.EudraCT number 2012-005397-63 ; date of registration 22 Nov 2012.

SUBMITTER: Robles NR

PROVIDER: S-EPMC5037621 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Robles Nicolás Roberto NR Peces Ramón R Gómez-Ferrer Álvaro Á Villacampa Felipe F Álvarez-Ossorio Jose Luis JL Pérez-Segura Pedro P Morote Juan J Herrera-Imbroda Bernardo B Nieto Javier J Carballido Joaquín J Anido Urbano U Valero Marian M Meseguer Cristina C Torra Roser R

Orphanet journal of rare diseases 20160926 1

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27669821

Similar Datasets

Project description:BackgroundEverolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be effective and safe in the treatment of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC). The Everolimus For Fast Expanded aCcess in TSC SEGA (EFFECTS) study was designed to provide everolimus access to patients with SEGA associated with TSC and to mainly assess the safety and also efficacy of everolimus in a real-world setting.MethodsEFFECTS was a phase 3b, open-label, noncomparative, multicenter, expanded access study. Eligible patients were ≥ 3 years of age, with a definite diagnosis of TSC, and with at least one SEGA lesion identified by MRI or CT scan. Patients received once daily everolimus (dose adjusted to attain a trough level of 5-15 ng/mL). Safety evaluation was the primary objective and included collection of adverse events (AEs) and serious AEs, with their severity and relationship to everolimus. Efficacy evaluation, which was the secondary objective, was based on the best overall response as per medical judgment.ResultsOf the 120 patients enrolled, 100 (83.3%) completed the study. Median age of patients was 11 years (range, 1-47). Median daily dose of everolimus was 5.82 mg (range, 2.0-11.8). Median duration of exposure was 56.5 weeks (range, 0.3-130). The overall incidence of AEs was 74.2%. Aphthous stomatitis (18 [15.0%]), pyrexia (18 [15.0%]), bronchitis (11 [9.2%]), and stomatitis (10 [8.3%]) were the most common AEs reported. Overall, 25 patients had grade 3 AEs; most frequent was stomatitis (4 [3.3%]). Grade 4 AEs were reported in three (2.5%) patients. A total of 62 (51.7%) patients had suspected drug-related AEs, of which 15 (12.5%) were of grade 3 or 4. In eight (6.7%) patients, AEs led to drug discontinuation. With regard to efficacy, 81 (67.5%) patients had a partial response, 35 (29.2%) had a stable disease, and one (0.8%) had progressive disease. The response was unknown in three (2.5%) patients.ConclusionThis study confirms the acceptable safety profile of everolimus in patients with SEGA associated with TSC in a real-world setting. The results further support the efficacy of everolimus in the treatment of SEGA associated with TSC. (EudraCT: 2010-022583-13).

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets