Exposure-response analysis as evidence for anti-tumor activity of everolimus in the treatment of patients with subependymal giant-cell astrocytoma (SEGA) associated with tuberous sclerosis (TS).

9550 Background: On October 29, 2010 the US FDA granted accelerated approval for the use of everolimus in the treatment of patients with SEGA associated with TS not amenable to curative surgical resection. Data from a single-arm trial (N=28 patients) was submitted for patients treated with a starting dose of 3 mg/m2/day of everolimus and subsequently titrated to a target steady-state blood trough concentration (Cminss) of 5–15 ng/ml. An exposure-response analysis of the results was conducted to examine whether: Everolimus demonstrates activity in SEGA, and; therapeutic window (5-15 ng/ml) is appropriate. Methods: Exposure-response analysis focused on the relationship between average Cminss within a patient during 6 months (exposure) and percent reduction from baseline SEGA tumor volume at six months (response). The distribution of Cminss along with the % of patients within the 5–15 ng/ml target range was also examined to explore appropriateness of therapeutic window. Results: Exposure (Cminss) data were d...