BRAF/MEK Dual Inhibitors Therapy in Progressive and Anaplastic Pleomorphic Xanthoastrocytoma: Case Series and Literature Review

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  • 1 St. Louis Children’s Hospital, Washington University School of Medicine, St. Louis, Missouri;
  • | 2 Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, Texas;
  • | 3 Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas;
  • | 4 Department of Neurology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas;
  • | 5 Department of Radiology, Louisiana State University Health Shreveport, Shreveport, Louisiana;
  • | 6 Chicago Medical School, Rosalind Franklin University of Medicine and Science, Chicago, Illinois;
  • | 7 Department of Pathology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas;
  • | 8 Memorial Hermann-Texas Medical Center, Houston, Texas;
  • | 9 Department of Radiology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas; and
  • | 10 Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Recurrent and anaplastic pleomorphic xanthoastrocytoma (r&aPXA) is a rare primary brain tumor that is challenging to treat. Two-thirds of PXA tumors harbor a BRAF gene mutation. BRAF inhibitors have been shown to improve tumor control. However, resistance to BRAF inhibition develops in most cases. Concurrent therapy with MEK inhibitors may improve tumor control and patient survival. In this study, we identified 5 patients diagnosed with BRAF-mutated PXA who received BRAF and MEK inhibitors over a 10-year interval at our institution. Patient records were evaluated, including treatments, adverse effects (AEs), outcomes, pathology, next-generation sequencing, and MRI. The median age was 22 years (range, 14–66 years), 60% male, and 60% anaplastic PXA. Median overall survival was 72 months (range, 19–112 months); 1 patient died of tumor-related hemorrhage while off therapy, and the other 4 experienced long-term disease control (21, 72, 98, and 112 months, respectively). Dual BRAF/MEK inhibitors were well tolerated, with only grade 1–2 AEs, including rash, neutropenia, fatigue, abdominal discomfort, and diarrhea. No grade 3–5 AEs were detected. A literature review was also performed of patients diagnosed with BRAF-mutated PXA and treated with BRAF and/or MEK inhibitors through August 2021, with a total of 32 cases identified. The median age was 29 years (range, 8–57 years) and the median PFS and OS were 8.5 months (range, 2–35 months) and 35 months (range, 10–80 months), respectively. The most common AEs were grade 1–2 fatigue and skin rash. Results of this case series and literature review indicate that dual-drug therapy with BRAF and MEK inhibitors for r&aPXA with BRAF V600E mutation may delay tumor progression without unexpected AEs.

Submitted October 5, 2021; final revision received June 19, 2022; accepted for publication June 20, 2022.

Disclosures: C. Ware has disclosed having stock/ownership interest in Pfizer Inc. N. Tandon has disclosed holding an executive position with/serving on a governing board for/being employed by Braingrade and Nervonik Inc. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was partially funded by the Dr. Marni Rose Foundation.

Correspondence: Jay-Jiguang Zhu, MD, PhD, The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, 6400 Fannin Street, Suite 2800, Houston, TX 77030. Email: jay.jiguang.zhu@uth.tmc.edu

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