Sustained response of three pediatric BRAFV600E mutated high-grade gliomas to combined BRAF and MEK inhibitor therapy

Stephanie A Toll; Hung N Tran; Jennifer Cotter; Alexander R Judkins; Benita Tamrazi; Jaclyn A Biegel; Girish Dhall; Nathan J Robison; Kaaren Waters; Palak Patel; Robert Cooper; Ashley S Margol

doi:10.18632/oncotarget.26560

Sustained response of three pediatric BRAF^V600E mutated high-grade gliomas to combined BRAF and MEK inhibitor therapy

Oncotarget. 2019 Jan 11;10(4):551-557. doi: 10.18632/oncotarget.26560.

Authors

Stephanie A Toll^#^{1

2}, Hung N Tran^#³, Jennifer Cotter^{2

4}, Alexander R Judkins^{2

4}, Benita Tamrazi^{2

5}, Jaclyn A Biegel^{2

4}, Girish Dhall^{1

2}, Nathan J Robison^{1

2}, Kaaren Waters¹, Palak Patel², Robert Cooper^#³, Ashley S Margol^#^{1

2}

Affiliations

¹ Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
² University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
³ Kaiser Permanente Southern California, Los Angeles, CA, USA.
⁴ Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
⁵ Department of Radiology and Imaging, Children's Hospital Los Angeles, Los Angeles, CA, USA.

^# Contributed equally.

Abstract

Outcomes for children with high-grade gliomas (HGG) remain dismal despite aggressive treatment strategies. The use of targeted therapy for BRAF^V600E mutated malignancies including HGG is being explored as a potentially well tolerated and effective therapeutic option. The results of adult melanoma studies demonstrating that combination therapy with BRAF inhibitors and MEK inhibitors results in prolonged survival led us to employ this treatment strategy in children with BRAF^V600E mutated HGG. In this case series, we describe three pediatric patients with HGG with confirmed BRAF^V600E mutation who demonstrated responses to combination therapy with dabrafenib and trametinib.

Keywords: BRAF mutation; high-grade glioma; pediatrics; targeted therapy.