Maintenance therapy with everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis (the EMINENTS study)
Everolimus is an mTOR inhibitor which is used in the treatment of patients with tuberous sclerosis (TS), specifically those with subependymal giant cell astrocytomas (SEGAs) which cannot be curatively resected. Current protocols involve daily treatment with everolimus on an ongoing basis, though it has been hypothesized that once the disease has stabilized that the dose may be reduced. This is an important consideration given that, while the short term side effects are considered acceptable, long term side effects of everolimus therapy remain less known. This study is a single arm prospective trial designed to evaluate the efficacy and safety of a dose reduced everolimus maintenance therapy following initial disease treatment and stabilization.
Ten patients with TS-related SEGAs were included in this trial. Following at least 12 months of treatment therapy with everolimus resulting in tumor reduction and stabilization, patients were given a reduced dose (3 doses/week rather than daily) of everolimus over the subsequent 12 months. The primary outcome was the proportion of patients with stable disease.
The tumors all increased in size after reduction in therapy but the increase occurred in the first 90 days after which there was stabilization. Given the a priori criterion for progression as a 50% increase in volume, this was not considered a statistically significant difference. No recurrence of symptoms from the tumors were noted. Adverse events were less severe and less frequent with reduced treatment compared with the daily standard everolimus treatment.
Limitations of this study include lack of randomization and very small patient cohort, a criterion for progression (50% tumor increase) which could be challenged, and the risk of noncompliance when the medication was only ordered for three times per week.