EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
Abstrakt
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 %]).