Clinical trials targeting neurofibromatoses-associated tumors: a systematic review

Author:

Roman Souza Gabriel1ORCID,Abdalla Ahmed1,Mahadevan Daruka1

Affiliation:

1. Institute for Drug Development, Division of Hematology and Medical Oncology, Mays Cancer Center, University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, Texas, USA

Abstract

Abstract Background There is a paucity of literature that comprehensively analyzes previous and current clinical trials targeting neurofibromatoses-related tumors. This article aims to provide readers with drug development efforts targeting these tumors by analyzing translational and clinical findings. Methods This systematic review was written according to the PRISMA guidelines. Inclusion criteria were clinical trials involving patients with neurofibromatosis type 1, type 2, or schwannomatosis that were treated with therapies targeting neurofibromatoses-associated tumors and that were registered on clinicaltrials.gov. In addition, a search was performed in PubMed, Web of Science, Google Scholar, and Embase European for articles fully describing these clinical trials. Results A total of 265 clinical trials were registered and screened for eligibility. Ninety-two were included in this systematic review involving approximately 4636 participants. The number of therapies analyzed was more than 50. Drugs under investigation mainly act on the MAPK/ERK and PI3K/AKT/mTOR pathways, tumor microenvironment, or aberrantly over-expressed cell surface receptors. Selumetinib was the most effective medication for treating a neurofibromatosis type 1-associated tumor with approximately 68%–71% partial response for inoperable or progressive plexiform neurofibromas in children 2 years of age and older and bevacizumab for a neurofibromatosis type 2-related tumor with approximately 36%–41% partial response for vestibular schwannomas in patients 12 years of age and older. Conclusions This systematic review presents the results of previous clinical investigations and those under development for neurofibromatoses-associated tumors. Clinicians may use this information to strategize patients to appropriate clinical trials.

Funder

National Cancer Institute

Publisher

Oxford University Press (OUP)

Subject

Electrical and Electronic Engineering,Building and Construction

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