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Phase II trial of lapatinib in adult and pediatric patients with neurofibromatosis type 2 and progressive vestibular schwannomas

Authors :
John G. Golfinos
Mari Hagiwara
Matthias A. Karajannis
Geneviève Legault
Kevin M. Koch
Marc S. Ballas
Annette O. Nusbaum
Krysten Brown
Jeffrey C. Allen
Tsivia Hochman
Judith D. Goldberg
J. Thomas Roland
Source :
Neuro-Oncology. 14:1163-1170
Publication Year :
2012
Publisher :
Oxford University Press (OUP), 2012.

Abstract

This single-institution phase II study was performed to estimate the response rate to lapatinib in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannoma (VS). Twenty-one eligible patients were enrolled. Brain and spine MRIs, including 3-dimensional volumetric tumor analysis, and audiograms were performed once at baseline and again every 12 weeks. The primary response end point was evaluable in 17 patients and defined as ≥15% decrease in VS volume. Hearing was evaluable as a secondary end point in 13 patients, with responses defined as an improvement in the pure tone average of at least 10 dB or a statistically significant increase in word recognition scores. Four of 17 evaluable patients experienced an objective volumetric response (23.5%; 95% confidence interval [CI], 10%–47%), with median time to response of 4.5 months (range, 3–12). In responders, reduction in VS volumes ranged from −15.7% to −23.9%. Four of 13 patients evaluable for hearing met hearing criteria for response (30.8%; 95% CI, 13%–58%). One sustained response exceeded 9 months in duration. Median time to overall progression (ie, volumetric progression or hearing loss) was 14 months. The estimated overall progression-free survival and volumetric progression-free survival at 12 months were 64.2% (95% CI, 36.9%–82.1%) and 70.6% (95% CI, 43.1%–86.6%), respectively. Toxicity was generally minor, and no permanent dose modifications were required. Lapatinib carries minor toxicity and has objective activity in NF2 patients with progressive VS, including volumetric and hearing responses. Future studies could explore combination therapy with other molecular targeted agents such as bevacizumab.

Details

ISSN :
15235866 and 15228517
Volume :
14
Database :
OpenAIRE
Journal :
Neuro-Oncology
Accession number :
edsair.doi.dedup.....0bd86f3b17ead61a8c52362239dcdeea
Full Text :
https://doi.org/10.1093/neuonc/nos146