Pham Lily C, Weller Lauryn, Gann Claudia N, Schumacher Karl Maria, Vlassak Soetkin, Swanson Todd, Highsmith Kaitlin, O'Brien Barbara J, Nash Sebnem, Aaroe Ashley, de Groot John F, Majd Nazanin K
Department of Neurology, University of Maryland, Baltimore, MD, United States.
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Oncologist. 2025 Jan 17;30(1). doi: 10.1093/oncolo/oyae100.
The prognosis of patients with glioblastoma (GBM) remains poor despite current treatments. Targeted therapy in GBM has been the subject of intense investigation but has not been successful in clinical trials. The reasons for the failure of targeted therapy in GBM are multifold and include a lack of patient selection in trials, the failure to identify driver mutations, and poor blood-brain barrier penetration of investigational drugs. Here, we describe a case of a durable complete response in a newly diagnosed patient with GBM with leptomeningeal dissemination and PTPRZ1-MET fusion who was treated with tepotinib, a brain-penetrant MET inhibitor. This case of successful targeted therapy in a patient with GBM demonstrates that early molecular testing, identification of driver molecular alterations, and treatment with brain-penetrant small molecule inhibitors have the potential to change the outcome in select patients with GBM.
尽管目前有多种治疗方法，但胶质母细胞瘤（GBM）患者的预后仍然很差。GBM的靶向治疗一直是深入研究的课题，但在临床试验中尚未取得成功。GBM靶向治疗失败的原因是多方面的，包括试验中患者选择不当、未能识别驱动突变以及研究药物的血脑屏障穿透性差。在此，我们描述了一例新诊断的伴有软脑膜播散且存在PTPRZ1-MET融合的GBM患者，使用可穿透血脑屏障的MET抑制剂替泊替尼治疗后获得持久完全缓解的病例。该GBM患者成功接受靶向治疗的案例表明，早期分子检测、识别驱动分子改变以及使用可穿透血脑屏障的小分子抑制剂进行治疗，有可能改变部分GBM患者的预后。
