Zeyen Thomas, Treiber Antonia, Schneider Matthias, Potthoff Anna-Laura, Schaub Christina, Roever Lea, Layer Julian P, Gkika Eleni, Vatter Hartmut, Paech Daniel, Radbruch Alexander, Schaefer Niklas, Herrlinger Ulrich, Weller Johannes
Department of Neurooncology, Center for Neurology and Center for Integrated Oncology (CIO), University Hospital Bonn, Bonn, Germany.
Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.
Neurooncol Adv. 2025 Apr 28;7(1):vdaf084. doi: 10.1093/noajnl/vdaf084. eCollection 2025 Jan-Dec.
The optimal salvage therapy for recurrent MGMT-methylated glioblastoma (GBM), IDH wildtype, remains undefined. While lomustine is often used in clinical trials and considered standard-of-care, cumulative toxicity precludes its use in patients previously treated with lomustine/temozolomide. The role of temozolomide rechallenge in this setting is unclear.
This monocentric retrospective study included 70 patients with MGMT-methylated GBM, IDH wildtype, who received lomustine/temozolomide as first-line therapy. Descriptive data on second-line therapies were collected, and therapy responses were assessed. Survival outcomes were evaluated using Kaplan-Meier analysis.
Of 55 patients with documented tumor progression, 40 patients received second-line therapy. The most frequently used systemic therapy was temozolomide ( = 33, 79% of patients with second-line therapy), with a median number of 6 cycles and hematotoxicity grade 3 or 4 observed in <20% of patients. Among patients receiving temozolomide only, stable disease or partial response was achieved in 53.3%, with a progression-free survival rate at 6 months after first recurrence of 50% and a 1-year OS rate of 45%.
Temozolomide rechallenge is a common, safe, and effective second-line option for patients with MGMT-methylated, IDH wildtype GBM following first-line lomustine/temozolomide therapy. These findings support its consideration as a salvage therapy in appropriate clinical scenarios.
对于复发性MGMT甲基化、异柠檬酸脱氢酶（IDH）野生型的胶质母细胞瘤（GBM），最佳挽救治疗方案仍未明确。虽然洛莫司汀常用于临床试验并被视为标准治疗方法，但累积毒性使其无法用于先前接受过洛莫司汀/替莫唑胺治疗的患者。在这种情况下，替莫唑胺再次挑战治疗的作用尚不清楚。
这项单中心回顾性研究纳入了70例MGMT甲基化、IDH野生型的GBM患者，这些患者接受洛莫司汀/替莫唑胺作为一线治疗。收集了二线治疗的描述性数据，并评估了治疗反应。使用Kaplan-Meier分析评估生存结局。
在55例记录有肿瘤进展的患者中，40例接受了二线治疗。最常用的全身治疗是替莫唑胺（n = 33，占二线治疗患者的79%），中位疗程为6个周期，<20%的患者出现3级或4级血液毒性。在仅接受替莫唑胺治疗的患者中，53.3%实现了病情稳定或部分缓解，首次复发后6个月的无进展生存率为50%，1年总生存率为45%。
对于一线接受洛莫司汀/替莫唑胺治疗的MGMT甲基化、IDH野生型GBM患者，替莫唑胺再次挑战治疗是一种常见、安全且有效的二线选择。这些发现支持在适当的临床情况下将其作为挽救治疗方法。
