title: EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex.
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.
  
  
  CONCLUSIONS
  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).
authors: Neurology Department, Bethesda Children's Hospital, Bethesda Street 3, H-1146, Budapest, Hungary. fog.andras@gmail.com.
authors: Andras
authors: A
authors: Fogarasi
authors: Gasthuisberg University Hospitals Leuven, Leuven, Belgium.
authors: Liesbeth
authors: L
authors: De Waele
authors: Pediatric Unit, University Hospital, Siena, Italy.
authors: Gabriella
authors: G
authors: Bartalini
authors: Children's Memorial Health Institute, Warsaw, Poland.|Department of Pediatric Neurology, Medical University of Warsaw, Warsaw, Poland.
authors: Sergiusz
authors: S
authors: Jozwiak
authors: Neonatology and NICU Section, DIMO, University of Bari, Bari, Italy.
authors: Nicola
authors: N
authors: Laforgia
authors: Ghent University Hospital, Ghent, Belgium.
authors: Helene
authors: H
authors: Verhelst
authors: Motol University Hospital, Prague, Czech Republic.
authors: Borivoj
authors: B
authors: Petrak
authors: CHU Pellegrin-Hôpital des Enfants, Bordeaux, France.
authors: Jean-Michel
authors: JM
authors: Pedespan
authors: German Cancer Research Center and Section of Pediatric Brain Tumors, University Hospital, Heidelberg, Germany.
authors: Olaf
authors: O
authors: Witt
authors: Novartis Farmacéutica SA, Barcelona, Spain.
authors: Ramon
authors: R
authors: Castellana
authors: Novartis Farma S.p.A., Origgio, Italy.
authors: Stefania
authors: S
authors: Crippa
authors: Novartis Farma S.p.A., Origgio, Italy.
authors: Gabriella
authors: G
authors: Gislimberti
authors: Neurology Department, Bethesda Children's Hospital, Bethesda Street 3, H-1146, Budapest, Hungary.|National Institute of Neurosciences, Budapest, Hungary.
authors: Zsuzsanna
authors: Z
authors: Gyorsok
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy*; D001932:Brain Neoplasms / Q000188:drug therapy*; D001991:Bronchitis / Q000139:chemically induced; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012449:Safety; D013280:Stomatitis / Q000139:chemically induced; D013281:Stomatitis, Aphthous / Q000139:chemically induced; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus
keywords: Everolimus; Expanded access program; Subependymal giant cell astrocytoma; Tuberous sclerosis