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

Clinical trial Everolimus Mammalian target of rapamycin (mTOR) inhibitors NF2 Quantitative imaging biomarkers Vestibular schwannoma

Journal

Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335

Informations de publication

Date de publication:
Apr 2024
Historique:
received: 28 12 2023
accepted: 01 02 2024
medline: 18 4 2024
pubmed: 19 2 2024
entrez: 19 2 2024
Statut: ppublish

Résumé

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. 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). 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. 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).

Identifiants

pubmed: 38372904
doi: 10.1007/s11060-024-04596-4
pii: 10.1007/s11060-024-04596-4
pmc: PMC11023969
doi:

Substances chimiques

Everolimus 9HW64Q8G6G
Biomarkers 0

Banques de données

ClinicalTrials.gov
['NCT01345136']

Types de publication

Clinical Trial, Phase II Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

339-348

Subventions

Organisme : Congressionally Directed Medical Research Programs
ID : W81XWH-12-1-0116

Informations de copyright

© 2024. The Author(s).

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Auteurs

Phioanh Leia Nghiemphu (PL)

Department of Neurology, UCLA Neuro‑Oncology Program, David Geffen School of Medicine and Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles, Los Angeles, CA, USA.

Jeremie Vitte (J)

Department of Head and Neck Surgery, David Geffen School of Medicine and Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles, 675 Charles E Young Dr. S, MRL 2240, Los Angeles, CA, 90095-7286, USA.

Eva Dombi (E)

Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, USA.

Thien Nguyen (T)

Department of Neurology, UCLA Neuro‑Oncology Program, David Geffen School of Medicine and Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles, Los Angeles, CA, USA.
Department of Pediatrics, Division of Pediatric Hematology, Oncology, Stem Cell Transplant and Regenerative Medicine, Stanford University, Palo Alto, CA, USA.

Naveed Wagle (N)

Department of Medicine, Division of Medical Oncology, Norris Cancer Center, University of Southern California, Los Angeles, CA, USA.
Department of Translational Neurosciences, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.

Akira Ishiyama (A)

Department of Head and Neck Surgery, David Geffen School of Medicine and Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles, 675 Charles E Young Dr. S, MRL 2240, Los Angeles, CA, 90095-7286, USA.

Ali R Sepahdari (AR)

Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Diagnostic Neuroradiology, Scripps Clinic Medical Group, La Jolla, CA, USA.

David Cachia (D)

Department of Neurosurgery, Division of Neuro-oncology, Medical University of South Carolina, Charleston, SC, USA.
Department of Medicine, Division of Hematology/Oncology, University of Massachusetts, Worcester, MA, USA.

Brigitte C Widemann (BC)

Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, USA.

Derald E Brackmann (DE)

Department of Otolaryngology and Neurotology, House Clinic and Research Institute, Los Angeles, CA, USA.

Joni K Doherty (JK)

Center for Neural Tumor Research, House Research Institute, Los Angeles, CA, USA.
Department of Otolaryngology - Head and Neck Surgery, University of Southern California, Los Angeles, CA, USA.

Michel Kalamarides (M)

Department of Neurosurgery, Hôpital Pitié-Salpêtrière, APHP, Sorbonne Université, Paris, France.

Marco Giovannini (M)

Department of Head and Neck Surgery, David Geffen School of Medicine and Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles, 675 Charles E Young Dr. S, MRL 2240, Los Angeles, CA, 90095-7286, USA. mgiovannini@mednet.ucla.edu.

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Classifications MeSH