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

A. Fogarasi, Liesbeth De Waele, Gabriella Bartalini, Sergiusz Jozwiak, Nicola Laforgia, Helene Verhelst, Borivoj Petrak, Jean Michel Pedespan, Olaf Witt, Ramon Castellana, Stefania Crippa, Gabriella Gislimberti, Zsuzsanna Gyorsok

Research output: Article

5 Citations (Scopus)

Abstract

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)

Original languageEnglish
Article number126
JournalBMC Neurology
Volume16
Issue number1
DOIs
Publication statusPublished - aug. 8 2016

Fingerprint

Tuberous Sclerosis
Astrocytoma
Stomatitis
Safety
Everolimus
Aphthous Stomatitis
Bronchitis
Sirolimus
Drug-Related Side Effects and Adverse Reactions
Fever

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

EFFECTS : An expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex. / Fogarasi, A.; 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.

In: BMC Neurology, Vol. 16, No. 1, 126, 08.08.2016.

Research output: Article

Fogarasi, A, De Waele, L, Bartalini, G, Jozwiak, S, Laforgia, N, Verhelst, H, Petrak, B, Pedespan, JM, Witt, O, Castellana, R, Crippa, S, Gislimberti, G & Gyorsok, Z 2016, 'EFFECTS: An expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex', BMC Neurology, vol. 16, no. 1, 126. https://doi.org/10.1186/s12883-016-0658-4
Fogarasi, A. ; 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. In: BMC Neurology. 2016 ; Vol. 16, No. 1.
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abstract = "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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T1 - EFFECTS

T2 - An expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex

AU - Fogarasi, A.

AU - De Waele, Liesbeth

AU - Bartalini, Gabriella

AU - Jozwiak, Sergiusz

AU - Laforgia, Nicola

AU - Verhelst, Helene

AU - Petrak, Borivoj

AU - Pedespan, Jean Michel

AU - Witt, Olaf

AU - Castellana, Ramon

AU - Crippa, Stefania

AU - Gislimberti, Gabriella

AU - Gyorsok, Zsuzsanna

PY - 2016/8/8

Y1 - 2016/8/8

N2 - 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)

AB - 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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KW - Expanded access program

KW - Subependymal giant cell astrocytoma

KW - Tuberous sclerosis

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