TR-13 * EFFECTS OF EVEROLIMUS ON MENINGIOMA GROWTH IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2

  • Osorio D
  • Filatov A
  • Hagiwara M
  • et al.
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Abstract

BACKGROUND: Vestibular schwannomas (VS) andmeningiomas are associated with biallelic loss of NF2, and may arise sporadically or in the context of the tumor predisposition syndrome neurofibromatosis type 2 (NF2). Loss of NF2 activates the mammalian target of rapamycin (mTOR) pathway, and published in vitro and in vivo data suggest that mTOR inhibition may be effective in the treatment of NF2-deficient VS and meningiomas. Everolimus is an oral inhibitor of mTOR complex 1 (mTORC1) with anti-tumor activity in a variety of neoplasms. METHOD(S): We conducted a review of adult and pediatric patients with NF2 and progressive VS treated with everolimus on our prospective phase II clinical trial (Clinical Trials.gov NCT01419639). Everolimus was administered at a daily dose of 10 mg in continuous 28-day courses for up to 12 courses. We included patients with at least one volumetrically measurable meningioma (>0.5 cc) who received at least six 28-day courses of therapy. Tumor response was assessed with brain MRI every three months using three dimensional volumetric analysis. RESULT(S): Three patients met inclusion criteria, with 10 evaluable meningiomas and a total combined volume of 11.84 cc at baseline (median 1.20 cc, range 0.53-3.00 cc). Median time on therapy was 9 months (range 6-12 months). Total combined meningioma volume remained stable during treatment (-1.8%). Correspondingly, none of the individual tumors analyzed met criteria for volumetric response or progression during the treatment period (range -10%to+9.4%). CONCLUSION(S): Neither objective response nor progression were observed inmeningiomas from NF2 patients during a median treatment duration of 9 months. Further clinical studies are required to determine whether everolimus may affect meningioma growth velocity. To better understand pharmacologic mTOR signaling pathway modulation in human VS and meningiomas in vivo, we are currently conducting a multicenter pharmacodynamic/pharmacokinetic ("phase 0") study with everolimus (ClinicalTrials.gov NCT01880749).

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APA

Osorio, D., Filatov, A., Hagiwara, M., Mitchell, C., Wisoff, J., Golfinos, J., … Karajannis, M. (2015). TR-13 * EFFECTS OF EVEROLIMUS ON MENINGIOMA GROWTH IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2. Neuro-Oncology, 17(suppl 3), iii39–iii39. https://doi.org/10.1093/neuonc/nov061.158

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