@article{a7efea0156f24cbbbd9c915ac2f57105,
title = "Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis-1 with Everolimus: A Phase II, Open-Label, Single-Arm Trial",
abstract = "Background: Cutaneous neurofibromas cause disfigurement and discomfort in individuals with neurofibromatosis type 1 (NF-1). Methods: The primary objective of this phase II, open-label, single-arm trial was to assess whether orally administered everolimus reduced the surface volume of cutaneous neurofibromas in patients with NF-1. Results: Of 22 patients who took the study drug, 17 completed the trial; 5 patients withdrew due to adverse events. Sixteen patients had photographs of sufficient quality for assessment of the primary outcome. A significant reduction in lesion surface volume, defined as an end of trial volume > 2 standard errors (SE) less than baseline volume, was observed for 4/31 lesions (13%) from 3/16 patients (19%). Additionally, a statistically significant absolute change in average height for paired lesions was observed (p = 0.048). Although not a prespecified outcome measure, a dramatic reduction in the size of 3 large plexiform neurofibromas with a cutaneous component was also noted and documented by measurement of maximum circumference or magnetic resonance imaging-based volumetric analysis. Adverse events were common in this trial, but no serious adverse events occurred. Conclusions: Although this was a small, exploratory trial that was not powered for significance, the reduction in surface volume observed in this study is noteworthy assuming that the natural course for untreated lesions is to maintain or increase in volume. Future studies are needed with larger study populations that incorporate longer durations of treatment and better standardization of volumetric measurements. Trial Registration ClinicalTrials.gov Identifier: NCT02332902.",
author = "Slopis, {John M.} and Octavio Arevalo and Bell, {Cynthia S.} and Hebert, {Adelaide A.} and Hope Northrup and Riascos, {Roy F.} and Samuels, {Joshua A.} and Smith, {Keri C.} and Patti Tate and Koenig, {Mary Kay}",
note = "Funding Information: We are indebted to the patients and families who participated in this trial. We also thank Matthew J. Scheible of the Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston for assistance with data verification, and Raye L. Alford, Ph.D., of Genetics Genomics Consulting LLC for assistance with the preparation of this manuscript. This study was supported by Novartis Pharmaceuticals (CRAD001CUS232T) and a research grant from the Texas Neurofibromatosis Foundation. John M. Slopis, Joshua A. Samuels, and Mary Kay Koenig report grants and personal fees from Novartis Pharmaceuticals. Keri C. Smith reports a grant from the Texas Neurofibromatosis Foundation. Joshua A. Samuels reports personal fees from MedStudy, Inc. Adelaide A. Hebert, Hope Northrup, and Mary Kay Koenig report provisional patents pending. John M. Slopis is employed by The University of Texas MD Anderson Cancer Center. Octavio Arevalo, Adelaide A. Hebert, Hope Northrup, Riascos, Joshua A. Samuels, Keri C. Smith, Mary Kay Koenig, Cynthia S. Bell, and Patti Tate are or were employed by The University of Texas Health Science Center at Houston at the time of this trial. Funding Information: Conflict of Interest John M. Slopis, Joshua A. Samuels, and Mary Kay Koenig report grants and personal fees from Novartis Pharmaceuticals. Keri C. Smith reports a grant from the Texas Neurofibromatosis Foundation. Joshua A. Samuels reports personal fees from MedStudy, Inc. Adelaide A. Hebert, Hope Northrup, and Mary Kay Koenig report provisional patents pending. John M. Slopis is employed by The University of Texas MD Anderson Cancer Center. Octavio Arevalo, Adelaide A. Hebert, Hope Northrup, Riascos, Joshua A. Samuels, Keri C. Smith, Mary Kay Koenig, Cynthia S. Bell, and Patti Tate are or were employed by The University of Texas Health Science Center at Houston at the time of this trial. Funding Information: Funding This study was supported by Novartis Pharmaceuticals (CRAD001CUS232T) and a research grant from the Texas Neurofibromatosis Foundation. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1007/s40268-018-0248-6",
language = "English (US)",
volume = "18",
pages = "295--302",
journal = "Drugs in R and D",
issn = "1174-5886",
publisher = "Adis International Ltd",
number = "4",
}