Originally developed to prevent rejection of transplanted organs, the mammalian target of rapamycin (mTOR) inhibitor everolimus dramatically reduced the volume of subependymal giant cell astrocytomas (SEGAs) in persons with tuberous sclerosis complex (TSC), a genetic disease that causes tumors to grow on vital organs.

In addition to helping prevent transplant rejection, everolimus is used in the treatment of renal cell carcinoma as well as SEGA. The FDA granted accelerated approval to everolimus for this brain tumor after a 2010 phase 2 study showed good results, recounts a statement from Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio, where David Neal Franz, MD, is codirector of the TSC clinic. Franz, who helped conduct the 2010 study, is the main author of the new report in The Lancet describing the phase 3 results.

Prior to FDA approval, surgery was considered the standard therapy for SEGA, but everolimus is a potential alternative to surgery and the first targeted medical therapy for TSC, noted Franz in the Children’s Hospital statement.

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In the phase 3 portion of the study, 117 patients ranging in age from infancy to 65 years (mean age 9.5 years) with TSC and SEGAs were randomized to receive either everolimus (78 patients) or placebo (39 patients).

None of the members of the placebo group had any reduction in SEGA volume, but 27 (35%) of the patients receiving everolimus experienced at least a 50% reduction in volume. Adverse events were mostly grade 1 or grade 2, the most common being mouth ulceration in 25 patients (32%) in the everolimus group and two (5%) in the placebo group, stomatitis (24 [31%] and 8 [21%], respectively), convulsion (18 [23%] and 10 [26%], respectively), and pyrexia (17 [22%] and 6 [15%], respectively). No patient discontinued treatment due to adverse events.