P08.62 Salvage chemotherapy with bevacizumab and fotemustine in temozolomide-pretreated patients with recurrent grade III gliomas: a phase II study

Abstract

AbstractIntroduction:Fotemustine is a nitrosourea with elevated lipophilic properties, that has shown activity as monotherapy in recurrent grade III gliomas, but few data are available on the association with the antiangiogenic drug bevacizumab.Method:From July 2008 to November 2015 we accrued, in this single arm phase II study, patients with an histological diagnosis of grade III glioma (according to WHO, 2007) at relapse after radiotherapy and/or temozolomide and we treated them with a combination of bevacizumab and fotemustine. The primary endpoint was 6-month progression-free survival (PFS-6), while secondary endpoints were overall survival (OS), disease control rate and toxicity.Results:Forty-six patients with grade III glioma (22 astrocytomas, 10 oligodendrogliomas and 14 oligoastrocytomas, 67% MGMT methylated and 30% 1p/19q codeleted) were enrolled. Median age was 45 years and KPS ≥ 90 in 54%. PFS-6, median PFS and OS were 45%, 5 months and 9 months, respectively. Nineteen patients (41%) had already received prior chemotherapy lines and 35% a second surgery before inclusion into the trial. We observed a 95% disease control rate (response or stable disease on MRI) after the induction phase with a neurological improvement in 40% and steroid reduction or withdrawal in 67%. In a preliminary analysis we didn’t observe significant differences in terms of clinical and/or radiological response rate, in PFS or OS according to MGMT methylation and 1p/19q codeletion status. There was a better clinical improvement in oligodendroglial subtype after induction phase (75% of patients), while no differences emerged in radiological disease control rate, PFS6, PFS or OS compared to astrocitary histotype. Survival rates of the whole cohort were 34% at 1 year, 21% at 2 years, 14% at 3 years, 7% at 4 years and 5% at 5 years. The pattern of progression was focal enhancing in 73% of tumors, diffuse non-enhancing (gliomatosis-like) in 12%, multicentric in 10% and local plus leptomeningeal in 5%.Twenty-two percent of patients discontinued fotemustine for grade 3/4 myelotoxicity. We did not observe any additional toxicity from the combination.Conclusions:The combination of bevacizumab and fotemustine as salvage treatment for grade III gliomas is safe and somewhat active in this heavily pretreated cohort. Further clinical studies should explore alternative regimens of therapy in the different molecular subgroups.