Effect of bevacizumab (BEV) and irinotecan (CPT-11) on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioblastoma (GBM) patients

Abstract

2026 Background: DCE-MRI can determine vascular permeability using Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space. We report a phase II trial to determine the correlation between vascular permeability and radiographic response in GBM patients treated with irinotecan and bevacizumab. Methods: Eligibility included 20 patients with recurrent GBM. Both agents were given every 14 days; bevacizumab at 10 mg/kg IV, and irinotecan at 340 mg/m2 for patients on enzyme inducing antiepileptic drugs (EIAED) and 125 mg/m2 for patients not on EIAED. Radiographic responses were assessed every 6 weeks. DCE-MRIs were performed before administration of chemotherapy, one day after treatment and after the first cycle. The primary endpoint was to examine the effect of bevacizumab and irinotecan treatment on vascular permeability as measured by percent change from baseline in Ktrans. Results: All 20 patients were enrolled, with a median age of 49.5 years. Best responses include one patient with complete response, nine with partial response (response rate=50%), nine patients with stable disease, and one with disease progression. A 6-month progression-free survival (PFS) of 65% and a 6-month overall survival (OS) of 85% were observed. Changes in Ktrans value were highly correlated with the percentage decline in tumor volume from baseline to end of cycle one (Spearman's rank correlation = 0.47; p=0.04). Using a two-sided t-test, borderline significant difference in mean Ktrans at 24 hours between responders and non-responders was obtained at six weeks (p=0.05). No DCE MRI measures at either 24 hours or 6 weeks were determined as predictors of PFS and OS. Fifteen patients discontinued therapy due to disease progression and two patients discontinued treatment due to toxicity (wound healing, n=1; pulmonary embolism, n=1). Conclusions: The utilization of DCE-MRI to determine a reduction in vascular permeability following a combination of bevacizumab and irinotecan is feasible and correlates with the degree of tumor volume decrease, but does not predict survival in this small study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech