No drug holidays in BRAF V600E glioma patients: An argument for dose reduction of targeted therapies.

Autor:	Bazer DA; National Cancer Institute, Neuro-Oncology Branch, National Institutes of Health, Bethesda, Maryland, USA.; Department of Neurology and Oncology, Johns Hopkins University, Baltimore, Maryland, USA., Kolchinski A; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Bush NAO; Departments of Neurology and Neurological Surgery, University of California San Francisco, San Francisco, California, USA., Clarke JL; Departments of Neurology and Neurological Surgery, University of California San Francisco, San Francisco, California, USA., Bagley SJ; Department of Medicine, Division of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Schreck KC; Department of Neurology and Oncology, Johns Hopkins University, Baltimore, Maryland, USA.
Jazyk:	angličtina
Zdroj:	Neuro-oncology practice [Neurooncol Pract] 2024 May 24; Vol. 11 (5), pp. 660-664. Date of Electronic Publication: 2024 May 24 (Print Publication: 2024).
DOI:	10.1093/nop/npae046
Abstrakt:	Background: Combined BRAF and MEK inhibition is effective for some BRAF V600E -altered gliomas, a cancer for which there are few effective therapies. While recent clinical trials demonstrate objective response rates of 30%-40%, tolerable adverse event rates are 70%-90%, and 12%-15% of patients stop therapy for toxicity. There are no clear guidelines regarding the timing and reinitiation of BRAF-targeted therapies following drug holidays. Here, we describe 4 patients with rapid disease progression during periods of treatment interruption. All patients experienced a response upon resumption of targeted therapy. Methods: This is a multi-institutional, retrospective review of 4 patients. Results: Three patients were diagnosed with BRAF V600E mutated anaplastic pleomorphic xanthoastrocytoma (aPXA) and 1 with epithelioid glioblastoma. The age range was 32 to 46; 3 patients were female and one patient was male. All patients were initially treated with radiation and were subsequently treated with BRAF/MEK inhibitors after disease progression. All patients with aPXA required the targeted therapy to be held due to toxicity and 1 patient held the therapy prior to transitioning to a novel BRAF-targeted agent. All patients were restarted on BRAF/MEK inhibitors after a drug holiday. Three patients required a dose reduction and all improved clinically following reinitiation. Conclusions: Clinical and radiographic progression may occur rapidly upon holding BRAF-targeted therapy, warranting judicious dose reductions and minimization of drug holidays. Competing Interests: There are none relevant to this work. Dr. Schreck: Consultant for Novartis, Springworks Therapeutics. Research funding from Springworks Therapeutics, FORE Biotherapeutics, and Pfizer DSMB for Advarra. Dr. Clarke: Consultant for Agios / Servier; Research funding from Agios / Servier and Merck. Dr. Bagley: Consulting and advisory boards: Telix, Servier, Bayer, Novocure. Research grants: Incyte, Novocure, GSK, Lilly, Kite. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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