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EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex

BACKGROUND: Everolimus, 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 d...

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Autores principales: Fogarasi, Andras, De Waele, Liesbeth, Bartalini, Gabriella, Jozwiak, Sergiusz, Laforgia, Nicola, Verhelst, Helene, Petrak, Borivoj, Pedespan, Jean-Michel, Witt, Olaf, Castellana, Ramon, Crippa, Stefania, Gislimberti, Gabriella, Gyorsok, Zsuzsanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976509/
https://www.ncbi.nlm.nih.gov/pubmed/27502586
http://dx.doi.org/10.1186/s12883-016-0658-4
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author Fogarasi, Andras
De Waele, Liesbeth
Bartalini, Gabriella
Jozwiak, Sergiusz
Laforgia, Nicola
Verhelst, Helene
Petrak, Borivoj
Pedespan, Jean-Michel
Witt, Olaf
Castellana, Ramon
Crippa, Stefania
Gislimberti, Gabriella
Gyorsok, Zsuzsanna
author_facet Fogarasi, Andras
De Waele, Liesbeth
Bartalini, Gabriella
Jozwiak, Sergiusz
Laforgia, Nicola
Verhelst, Helene
Petrak, Borivoj
Pedespan, Jean-Michel
Witt, Olaf
Castellana, Ramon
Crippa, Stefania
Gislimberti, Gabriella
Gyorsok, Zsuzsanna
author_sort Fogarasi, Andras
collection PubMed
description BACKGROUND: Everolimus, 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. METHODS: EFFECTS 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. RESULTS: Of 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. CONCLUSION: This 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)
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spelling pubmed-49765092016-08-09 EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex Fogarasi, Andras De Waele, Liesbeth Bartalini, Gabriella Jozwiak, Sergiusz Laforgia, Nicola Verhelst, Helene Petrak, Borivoj Pedespan, Jean-Michel Witt, Olaf Castellana, Ramon Crippa, Stefania Gislimberti, Gabriella Gyorsok, Zsuzsanna BMC Neurol Research Article BACKGROUND: Everolimus, 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. METHODS: EFFECTS 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. RESULTS: Of 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. CONCLUSION: This 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) BioMed Central 2016-08-08 /pmc/articles/PMC4976509/ /pubmed/27502586 http://dx.doi.org/10.1186/s12883-016-0658-4 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Fogarasi, Andras
De Waele, Liesbeth
Bartalini, Gabriella
Jozwiak, Sergiusz
Laforgia, Nicola
Verhelst, Helene
Petrak, Borivoj
Pedespan, Jean-Michel
Witt, Olaf
Castellana, Ramon
Crippa, Stefania
Gislimberti, Gabriella
Gyorsok, Zsuzsanna
EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
title EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
title_full EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
title_fullStr EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
title_full_unstemmed EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
title_short EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
title_sort effects: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976509/
https://www.ncbi.nlm.nih.gov/pubmed/27502586
http://dx.doi.org/10.1186/s12883-016-0658-4
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