Abstract 3701: Phase II study of BIBF1120 in recurrent glioblastoma multiforme

Background: BIBF 1120, a potent, orally available triple angiokinase inhibitor targeting VEGFR 1-3, PDGFR- α/-α, and FGFR 1-3, has shown promising clinical activity with a good safety profile in patients with advanced non-small cell lung cancer or ovarian cancer. The specific and simultaneous abrogation of these three pathways results in effective growth inhibition of both endothelial and perivascular cells. This may be more effective than inhibition of endothelial cell growth via the VEGF pathway alone. In addition, signalling via FGF-receptors has been identified as a possible escape mechanism for tumour angiogenesis when the VEGF pathway is disrupted. Recurrent glioblastomas (GBM) have an extremely poor prognosis and consequently new and innovative therapies are still needed. Accordingly, the purpose of this study was to assess the efficacy and safety of BIBF 1120 in two parallel groups of patients with recurrent GBM after radiotherapy and temozolomide (STD) or the same regimen and subsequent bevacizumab based therapy (BEV). Methods: Patients were included in one of two parallel groups depending of prior exposure to bevacizumab (STD or BEV). Inclusion critieria included recurrent GBM, PS 0-1, normal organ function, available archival tissue blocks, and measurable disease according to RANO guidelines. A total of 32 patients were to be enrolled in each group in a two-stage design including a stopping rule if less than 4/16 patient responded. BIBF-1120 was administered orally 200 mg bid, with weekly plasma sampling for the first 4 weeks and MRI assessement every 8 weeks. Primary endpoint was objective response rate. Secondary endpoints were safety, PFS and plasma and tissue biomarkers. Results: The study was prematurely stopped for after inclusion of 13 patients in the STD arm and 12 patients in the BEV arm. No objective responses were seen in either arm. One patient in the BEV arm has had stable disease for 8 months while the remainder of the patients in both arms progressed within the first 4 cycles. BIBF-1120 was very well tolerated with no observed grade III or IV adverse events. Most frequent adverse events were grade I-II hypertension, diarrhoea and fatigue, with a frequency of Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3701. doi:1538-7445.AM2012-3701