Response to imatinib as a function of target kinase expression in recurrent glioblastoma

Despite some progress in the treatment of glioblastoma, most patients experience tumor recurrence. Imatinib mesylate, a tyrosine kinase inhibitor of platelet derived growth factor receptor-alpha and -beta, c-fms, c-kit, abl and arg kinase (imatinib targets), has been shown to prevent tumor progression in early studies of recurrent gliomas, but has shown weak activity in randomized controlled trials. We studied the response to oral imatinib in 24 patients with recurrent glioblastoma who showed immunohistochemical expression of these imatinib targets in the initially resected tumor tissue.

We offered oral imatinib, 400 mg once daily treatment to 24 recurrent glioblastoma patients whose initial biopsy showed presence of at least one imatinib inhibitable tyrosine kinase.

Six imatinib treated patients survived over one year. Twelve patients achieved at least tumor stabilisations from 2.6 months to 13.4 months. Median progression free survival was 3 months and median overall survival was 6 months. Imatinib was well tolerated. We found evidence, though not statistically significant, that arg kinase [Abl-2] immunopositivity had shorter survival [5 months] than the arg kinase immunonegative group [9 months].

Responses to imatinib observed in this patient series where imatinib inhibitable tyrosine kinases were documented on the original biopsy are marginally better than that previously reported in imatinib treatment of unselected recurrent glioblastoma patients. We thus present a suggestion for defining a patient sub-population who might potentially benefit from imatinib.