Efficacy and safety of bevacizumab plus irinotecan in patients with recurrent malignant poor-prognosis glioma.

Abstract

e12555 Background: There is currently no standard of care for recurrent glioblastoma multiforme (GBM), although the anti-VEGF monoclonal antibody bevacizumab (Bev) has shown efficacy in conjunction with irinotecan (Iri). We present a retrospective analysis of patients with recurrent malignant brain tumors treated with Bev-Iri at our clinic. Methods: 37 adult patients with recurrent malignant brain tumors were included. Patient characteristics: median age 46 years, GBM diagnosis n = 26, other brain tumor histology n = 11. Prior surgery n = 34, prior chemotherapy n = 37, prior radiotherapy n = 32. Patients received Bev 10 mg/kg i.v. and Iri 125 mg/m2 i.v. (340 mg/m2 in one patient receiving enzyme-inducing antiepileptic drugs) every 14 days. Treatment was stopped on progression, patient's wish or physician's decision. Response was assessed using MacDonald's criteria on post-contrast MRI with inclusion of FLAIR, T2 and perfusion-weighted MRI. Adverse events (AEs) were monitored throughout therapy. Results: Patients received a median of 7 cycles of Bev-Iri (range 3–15) and 8 patients received maintenance Bev until progression. 26 patients (70%) achieved a complete or partial response with Bev-Iri, and 4 (11%) had stable disease. Median time to progression was 5.8 months (range 1.4–not reached) and median overall survival was 11.1 months (range 2.7–not reached) without difference between GBM patients and the group with other types of malignant brain tumors. The bevacizumab/irinotecan combination was well tolerated, with few grade 3 AEs (8 lymphocytopenia, 2 leucocytopenia, 1 diarrhea); there were no AEs of grade > 3. The most common grade 1–2 AEs were leucocytopenia (n = 7), hypertension (n = 5) and lymphocytopenia (n = 4). Conclusions: Our data show that bevacizumab plus irinotecan is an effective combination for recurrent malignant brain tumors and correspond with Phase II data for this strategy. The median overall survival of over 11 months in our study represents a considerable improvement in prognosis for these patients and warrants a larger, more thorough prospective exploration of this combination. The potential for bevacizumab-containing maintenance regimens also exists. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche