Targeted therapies in patients with newly diagnosed glioblastoma-A systematic meta-analysis of randomized clinical trials.

Autor: Scherm A; Wilhelm Sander-NeuroOncology Unit and Department of Neurology, Regensburg University Hospital, Regensburg, Germany., Ippen FM; Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany., Hau P; Wilhelm Sander-NeuroOncology Unit and Department of Neurology, Regensburg University Hospital, Regensburg, Germany., Baurecht H; Institute of Epidemiology and Preventive Medicine, Regensburg University Hospital, Regensburg, Germany., Wick W; Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.; German Cancer Research Center (DKFZ) & German Cancer Center (DKTK), Heidelberg, Germany., Gempt J; Department of Neurosurgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany., Knüttel H; University Library, Regensburg University, Regensburg, Germany., Leitzmann MF; Institute of Epidemiology and Preventive Medicine, Regensburg University Hospital, Regensburg, Germany., Seliger C; Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2023 Jun 01; Vol. 152 (11), pp. 2373-2382. Date of Electronic Publication: 2023 Jan 30.
DOI: 10.1002/ijc.34433
Abstrakt: Glioblastoma (GB) is the most common malignant primary brain tumor in adults. The standard of care for newly diagnosed GB involves surgical resection followed by radiochemotherapy with temozolomide, with or without tumor-treating fields. In recent years, various efforts have been made to identify suitable molecularly targeted treatment options for malignant brain tumors. This meta-analysis provides an overview of recently published randomized controlled trials (RCTs) with and without molecular stratification, analyzing targeted agents in patients with newly diagnosed GB. The Cochrane Library, MEDLINE (Ovid), ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform, and Google Scholar were searched for RCTs on targeted therapies in patients with newly diagnosed glioblastoma. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted and pooled in a random-effects meta-analysis. Twelve RCTs (n = 3941 patients) involving protein kinase inhibitors, proteasome and histone deacetylase inhibitors, anti-angiogenic approaches and poly (ADP-ribose) polymerase (PARP) inhibitors were included in the meta-analysis. None of the targeted agents achieved a significant benefit with regard to OS (HR = 0.98 [95% confidence interval (CI) 0.86-1.11, P = .7731]). By comparison, targeted therapy showed a benefit for PFS (HR = 0.83 [95% CI 0.74-0.94, P = .0037]), especially for patients with an unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter (0.75 [95% CI 0.56-0.99, P = .0440]). Prolongation of PFS was largely driven by VEGF inhibition with bevacizumab (HR = 0.70 [95% CI 0.61-0.80, P = .0000]). VEGF inhibition with bevacizumab prolonged PFS in patients with newly diagnosed glioblastoma compared to standard care. However, no improvement in OS was observed with any of the targeted agents.
(© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
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