Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill, North Carolina.
Department of Practice Advancement and Clinical Education, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina.
J Natl Compr Canc Netw. 2022 Sep;20(9):966-971. doi: 10.6004/jnccn.2022.7030.
Glioblastoma (GBM) is a malignant central nervous system neoplasm that remains largely incurable. Limited treatment options currently exist after disease progression on standard-of-care first-line therapy. However, repurposing the use of approved therapies in patients with potentially targetable genomic alterations continues to be an emerging area of interest. This report presents the first description of a patient with isocitrate dehydrogenase wild-type GBM with an underlying RET amplification who demonstrated a near-complete response while receiving therapy with the RET inhibitor selpercatinib. The case highlights the excellent blood-brain barrier penetration of selpercatinib, as well as its potential role in the management of RET-amplified GBM. Larger biomarker-enriched studies are needed to confirm the results of this case report. Given the rare incidence of RET alterations in GBM, findings from this report can help guide and support optimal treatment strategies for patients with RET-altered GBM.
胶质母细胞瘤（GBM）是一种恶性中枢神经系统肿瘤，目前基本上仍无法治愈。在标准一线治疗疾病进展后，目前的治疗选择有限。然而，重新利用在具有潜在可靶向基因组改变的患者中已批准的治疗方法仍然是一个新兴的研究领域。本报告首次描述了一名患有野生型 IDH 的 GBM 患者，其存在 RET 扩增，在接受 RET 抑制剂塞尔帕替尼治疗时表现出近乎完全缓解。该病例突出了塞尔帕替尼良好的血脑屏障穿透性，以及其在管理 RET 扩增型 GBM 中的潜在作用。需要更大的生物标志物富集研究来证实本病例报告的结果。鉴于 RET 改变在 GBM 中的罕见发生率，本报告的结果可以帮助指导和支持 RET 改变的 GBM 患者的最佳治疗策略。
