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Open Access 19-02-2024 | Vestibular Schwannoma | Case Study

Imaging as an early biomarker to predict sensitivity to everolimus for progressive NF2-related vestibular schwannoma

Authors: Phioanh Leia Nghiemphu, Jeremie Vitte, Eva Dombi, Thien Nguyen, Naveed Wagle, Akira Ishiyama, Ali R. Sepahdari, David Cachia, Brigitte C. Widemann, Derald E. Brackmann, Joni K. Doherty, Michel Kalamarides, Marco Giovannini

Published in: Journal of Neuro-Oncology | Issue 2/2024

Abstract

Purpose

NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory.

Methods

The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL).

Results

Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores.

Conclusions

Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011).

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Afinitor [package insert] (2022) Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

Title: Imaging as an early biomarker to predict sensitivity to everolimus for progressive NF2-related vestibular schwannoma
Authors: Phioanh Leia Nghiemphu
Jeremie Vitte
Eva Dombi
Thien Nguyen
Naveed Wagle
Akira Ishiyama
Ali R. Sepahdari
David Cachia
Brigitte C. Widemann
Derald E. Brackmann
Joni K. Doherty
Michel Kalamarides
Marco Giovannini
Publication date: 19-02-2024
Publisher: Springer US
Keywords: Vestibular Schwannoma
Vestibular Schwannoma
Everolimus
Biomarkers
Published in: Journal of Neuro-Oncology / Issue 2/2024
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-024-04596-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Imaging as an early biomarker to predict sensitivity to everolimus for progressive NF2-related vestibular schwannoma

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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