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

View Article: PubMed Central - PubMed

ABSTRACT

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.

Trial registration: EudraCT number 2012-005397-63; date of registration 22 Nov 2012.

No MeSH data available.


Related in: MedlinePlus

Reductions from baseline in renal angiomyolipoma volume in each study visit. The study ended as per protocol 1 year after first patient enrolment, which explains the reduced number of patients available at month 12
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Fig2: Reductions from baseline in renal angiomyolipoma volume in each study visit. The study ended as per protocol 1 year after first patient enrolment, which explains the reduced number of patients available at month 12

Mentions: The sum of volumes of all target AML lesions decreased in 16 (84.2 %) patients, including ≥30 % reduction from baseline in 11 (57.9 %) patients and ≥50 % in nine (47.4 %) patients; the proportion of patients achieving ≥30 % and ≥50 % reduction from baseline in each study visit is summarized in Fig. 2. Only three (15.8 %) patients report increased volumes, which were lower than 15 % in all cases.Fig. 2


Everolimus safety and efficacy for renal angiomyolipomas associated with tuberous sclerosis complex: a Spanish expanded access trial
Reductions from baseline in renal angiomyolipoma volume in each study visit. The study ended as per protocol 1 year after first patient enrolment, which explains the reduced number of patients available at month 12
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5037621&req=5

Fig2: Reductions from baseline in renal angiomyolipoma volume in each study visit. The study ended as per protocol 1 year after first patient enrolment, which explains the reduced number of patients available at month 12
Mentions: The sum of volumes of all target AML lesions decreased in 16 (84.2 %) patients, including ≥30 % reduction from baseline in 11 (57.9 %) patients and ≥50 % in nine (47.4 %) patients; the proportion of patients achieving ≥30 % and ≥50 % reduction from baseline in each study visit is summarized in Fig. 2. Only three (15.8 %) patients report increased volumes, which were lower than 15 % in all cases.Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

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.

Trial registration: EudraCT number 2012-005397-63; date of registration 22 Nov 2012.

No MeSH data available.


Related in: MedlinePlus