PMID- 36351333 OWN - NLM STAT- MEDLINE DCOM- 20221117 LR - 20240103 IS - 1540-1413 (Electronic) IS - 1540-1405 (Linking) VI - 20 IP - 11 DP - 2022 Nov TI - BRAF/MEK Dual Inhibitors Therapy in Progressive and Anaplastic Pleomorphic Xanthoastrocytoma: Case Series and Literature Review. PG - 1193-1202.e6 LID - 10.6004/jnccn.2022.7046 [doi] AB - 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. FAU - Kata, Karolina AU - Kata K AD - 1St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri. AD - 2Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, Texas. FAU - Rodriguez-Quintero, Juan C AU - Rodriguez-Quintero JC AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 4Department of Neurology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. FAU - Arevalo, Octavio D AU - Arevalo OD AD - 5Department of Radiology, Louisiana State University Health Shreveport, Shreveport, Louisiana. FAU - Zhang, Jackie J AU - Zhang JJ AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 6Chicago Medical School, Rosalind Franklin University of Medicine and Science, Chicago, Illinois. FAU - Bhattacharjee, Meenakshi Bidwai AU - Bhattacharjee MB AD - 7Department of Pathology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 8Memorial Hermann-Texas Medical Center, Houston, Texas. FAU - Ware, Cornelius AU - Ware C AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. FAU - Dono, Antonio AU - Dono A AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 8Memorial Hermann-Texas Medical Center, Houston, Texas. FAU - Riascos-Castaneda, Roy AU - Riascos-Castaneda R AD - 8Memorial Hermann-Texas Medical Center, Houston, Texas. AD - 9Department of Radiology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas; and. FAU - Tandon, Nitin AU - Tandon N AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 8Memorial Hermann-Texas Medical Center, Houston, Texas. FAU - Blanco, Angel AU - Blanco A AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 8Memorial Hermann-Texas Medical Center, Houston, Texas. FAU - Esquenazi, Yoshua AU - Esquenazi Y AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 8Memorial Hermann-Texas Medical Center, Houston, Texas. FAU - Ballester, Leomar Y AU - Ballester LY AD - 7Department of Pathology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 10Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Amsbaugh, Mark AU - Amsbaugh M AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 8Memorial Hermann-Texas Medical Center, Houston, Texas. FAU - Day, Arthur L AU - Day AL AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 8Memorial Hermann-Texas Medical Center, Houston, Texas. FAU - Zhu, Jay-Jiguang AU - Zhu JJ AD - 3Vivian L. Smith Department of Neurosurgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 4Department of Neurology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas. AD - 8Memorial Hermann-Texas Medical Center, Houston, Texas. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Natl Compr Canc Netw JT - Journal of the National Comprehensive Cancer Network : JNCCN JID - 101162515 RN - EC 2.7.11.1 (BRAF protein, human) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Young Adult MH - *Astrocytoma/drug therapy/genetics MH - *Brain Neoplasms/pathology MH - Fatigue MH - Mitogen-Activated Protein Kinase Kinases/genetics/therapeutic use MH - Mutation MH - Neoplasm Recurrence, Local MH - Protein Kinase Inhibitors/adverse effects MH - Proto-Oncogene Proteins B-raf/genetics MH - Adolescent MH - Middle Aged MH - Aged OTO - NOTNLM OT - BRAF V600E mutation OT - BRAF inhibitors OT - MEK inhibitors OT - Targeted drug therapy OT - pleomorphic xanthoastrocytoma (PXA) OT - rare brain tumors EDAT- 2022/11/10 06:00 MHDA- 2022/11/15 06:00 CRDT- 2022/11/09 18:14 PHST- 2021/10/05 00:00 [received] PHST- 2022/06/20 00:00 [accepted] PHST- 2022/11/09 18:14 [entrez] PHST- 2022/11/10 06:00 [pubmed] PHST- 2022/11/15 06:00 [medline] AID - 10.6004/jnccn.2022.7046 [doi] PST - ppublish SO - J Natl Compr Canc Netw. 2022 Nov;20(11):1193-1202.e6. doi: 10.6004/jnccn.2022.7046.