P17.17.A PERSONALISED SYSTEMIC THERAPY OF RECURRENT PRIMARY MALIGNANT BRAIN TUMOURS: REAL-WORLD SINGLE CENTRE EXPERIENCE

Abstract BACKGROUND Primary malignant brain tumours comprise a heterogeneous group of neoplasms characterised by poor responsiveness to standard therapies and limited immunogenicity. While first-line treatment protocols are well established, therapeutic standards for disease recurrence remain poorly defined. In selected cases, off-label therapies targeting specific molecular alterations may be considered based on tumour profiling. MATERIAL AND METHODS A retrospective analysis was conducted on patients with recurrent primary malignant brain tumours who received off-label molecularly targeted systemic therapies following exhausting of standard treatment options. Patients treated at the Institute of Oncology Ljubljana between 2021 and 2025 were included. Tumour molecular characterization was performed using Next Generation Sequencing (NGS). Clinical outcomes and adverse events were collected through systematic review of medical records. RESULTS Thirty patients receiving a total of 33 targeted therapies were included. Most frequent tumour entities were glioblastoma, astrocytoma and meningioma. Targeted therapies were directed against VEGF (bevacizumab), somatostatin receptors (octreotide), IDH1 mutations (ivosidenib), VEGFR/PDGFR kinases (regorafenib, cabozantinib), PDGFR/c-KIT (imatinib), BRAF V600E mutations (dabrafenib/trametinib), and NTRK fusions (larotrectinib). The mean therapy duration was 5.8 months (range 2-15 months). At first follow-up MRI (on average after 2.9 months), complete response was observed in 3.3% of patients, partial response in 10.0%, stable disease in 40.0%, and progressive disease in 3.3%. In the remaining cases, disease progression in 3.3% or response in 10.0% was assessed clinically. No fatal treatment-related adverse events were reported. Therapy discontinuation due to toxicity (CTCAE grade 5) occurred in one patient. Median progression-free survival (PFS) and overall survival (OS) were 6.9 and 9.3 months, respectively, in patients achieving at least stable disease, and 2.9 and 7.4 months, respectively, in those with disease progression at first follow-up. CONCLUSION Off-label targeted therapies based on molecular profiling demonstrated clinical activity and acceptable tolerability in patients with recurrent primary malignant brain tumours. Disease control, achieved in over half of cases, translated into prolonged survival. These findings support further evaluation and potential integration of personalised targeted therapies into clinical practice.