PMID- 27502586 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20181202 IS - 1471-2377 (Electronic) IS - 1471-2377 (Linking) VI - 16 DP - 2016 Aug 8 TI - EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex. PG - 126 LID - 10.1186/s12883-016-0658-4 [doi] LID - 126 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). FAU - Fogarasi, Andras AU - Fogarasi A AD - Neurology Department, Bethesda Children's Hospital, Bethesda Street 3, H-1146, Budapest, Hungary. fog.andras@gmail.com. FAU - De Waele, Liesbeth AU - De Waele L AD - Gasthuisberg University Hospitals Leuven, Leuven, Belgium. FAU - Bartalini, Gabriella AU - Bartalini G AD - Pediatric Unit, University Hospital, Siena, Italy. FAU - Jozwiak, Sergiusz AU - Jozwiak S AD - Children's Memorial Health Institute, Warsaw, Poland. AD - Department of Pediatric Neurology, Medical University of Warsaw, Warsaw, Poland. FAU - Laforgia, Nicola AU - Laforgia N AD - Neonatology and NICU Section, DIMO, University of Bari, Bari, Italy. FAU - Verhelst, Helene AU - Verhelst H AD - Ghent University Hospital, Ghent, Belgium. FAU - Petrak, Borivoj AU - Petrak B AD - Motol University Hospital, Prague, Czech Republic. FAU - Pedespan, Jean-Michel AU - Pedespan JM AD - CHU Pellegrin-Hopital des Enfants, Bordeaux, France. FAU - Witt, Olaf AU - Witt O AD - German Cancer Research Center and Section of Pediatric Brain Tumors, University Hospital, Heidelberg, Germany. FAU - Castellana, Ramon AU - Castellana R AD - Novartis Farmaceutica SA, Barcelona, Spain. FAU - Crippa, Stefania AU - Crippa S AD - Novartis Farma S.p.A., Origgio, Italy. FAU - Gislimberti, Gabriella AU - Gislimberti G AD - Novartis Farma S.p.A., Origgio, Italy. FAU - Gyorsok, Zsuzsanna AU - Gyorsok Z AD - Neurology Department, Bethesda Children's Hospital, Bethesda Street 3, H-1146, Budapest, Hungary. AD - National Institute of Neurosciences, Budapest, Hungary. LA - eng SI - EudraCT/2010-022583-13 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20160808 PL - England TA - BMC Neurol JT - BMC neurology JID - 100968555 RN - 0 (Antineoplastic Agents) RN - 9HW64Q8G6G (Everolimus) SB - IM MH - Adolescent MH - Adult MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Astrocytoma/*drug therapy MH - Brain Neoplasms/*drug therapy MH - Bronchitis/chemically induced MH - Child MH - Child, Preschool MH - Disease Progression MH - Everolimus/adverse effects/*therapeutic use MH - Female MH - Fever/chemically induced MH - Humans MH - Infant MH - Male MH - Middle Aged MH - Remission Induction MH - Safety MH - Stomatitis/chemically induced MH - Stomatitis, Aphthous/chemically induced MH - Treatment Outcome MH - Tuberous Sclerosis/*drug therapy MH - Young Adult PMC - PMC4976509 OTO - NOTNLM OT - Everolimus OT - Expanded access program OT - Subependymal giant cell astrocytoma OT - Tuberous sclerosis EDAT- 2016/08/10 06:00 MHDA- 2016/12/15 06:00 PMCR- 2016/08/08 CRDT- 2016/08/10 06:00 PHST- 2016/01/07 00:00 [received] PHST- 2016/08/02 00:00 [accepted] PHST- 2016/08/10 06:00 [entrez] PHST- 2016/08/10 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2016/08/08 00:00 [pmc-release] AID - 10.1186/s12883-016-0658-4 [pii] AID - 658 [pii] AID - 10.1186/s12883-016-0658-4 [doi] PST - epublish SO - BMC Neurol. 2016 Aug 8;16:126. doi: 10.1186/s12883-016-0658-4.