Neues aus der Neuroonkologie

Zusammenfassung

Im Rahmen der Entwicklung wirksamer Therapieverfahren bei der Behandlung maligner Gliome sind neue molekulare Prognose- und Therapiemarker ebenso wie systemorientierte und immunvermittelte Therapien auf dem Vormarsch. Der kombinierte Allelverlust am Chromosom 1p und 19q (LOH 1p19q), Mutationen der Isozitratdehydrogenase (IDH) und die Methylierung des Promoters der O⁶-Methylguanin-DNA-Methyltransferase (MGMT) beeinflussen mehr und mehr die Diagnosestellung und therapeutische Stratifizierung von Gliomen. Mehrere antiangiogenetische Substanzen wurden in großen Phase-III-Studien evaluiert. Dabei zeigte der Integrin-Inhibitor Cilengitide für den primären Endpunkt Gesamtüberleben keinen signifikanten Vorteil gegenüber der Standardtherapie. Der Inhibitor der Rezeptor-Tyrosinkinase des vascular endothelial growth factors (VEGF), Cediranib, enttäuschte in der REGAL-Studie. Die Entwicklung beider Substanzen wurde inzwischen eingestellt. Die Ergebnisse des humanisierten Antikörpers gegen VEGF, Bevacizumab, stehen in endgültiger Version noch aus. Jedoch wurde in einer als Abstract veröffentlichten Auswertung für den Ko-Endpunkt progressionsfreies Überleben eine Überlegenheit berichtet. In der Immuntherapie ist noch dieses Jahr auch in Europa eine multizentrische Phase-III-Studie geplant (ACT IV), die die Wirksamkeit von Rindopepimut, einem synthetisch hergestellten Immunepitop der mutierten Form des epidermal growth factor receptors (EGFRvIII), in der Primärtherapie des Glioblastoms untersucht.

Abstract

Within the framework of developing effective new therapies for the treatment of malignant gliomas, novel molecular prognostic and diagnostic markers as well as system-oriented and immune-mediated therapies are on the rise. The combined loss of heterogeneity of chromosome arms 1p and 19q (LOH 1p19q), mutations in the enzyme isocitrate dehydrogenase (IDH) and methylation of the O⁶-methylguanine-methyltransferase (MGMT) promoter are increasingly influencing the diagnostic evaluation and therapeutic stratification of gliomas. Several antiangiogenic agents have been evaluated in big multicenter trials. The integrin inhibitor cilengitide showed no significant effect on the primary endpoint, overall survival. The inhibitor of the receptor tyrosine kinase of the vascular endothelial growth factor (VEGF), cediranib, disappointed in the REGAL trial. The development of both substances was stopped by the companies. Final results for the humanized antibody against VEGF, bevacizumab, are pending, however, the co-primary endpoint, progression free survival, showed promising results in a first publication in abstract form. In the field of immunotherapy, a international phase III multicenter trial (ACT IV) will evaluate the efficacy of rindopepimut, a vaccine against mutant epidermal growth factor receptor variant III (EGFRvIII), in the treatment of glioblastoma.

Schlüsselwörter

Onkologie - Neuroonkologie - Gliome

Keywords

oncology - neurooncology - glioma

• Literatur

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