O10.05 * Final Analysis of the Belob Trial (A Randomized Phase Ii Study on Bevacizumab Versus Bevacizumab Plus Lomustine Versus Lomustine Single Agent in Recurrent Glioblastoma) and First Radiology Review Results

Abstract

INTRODUCTION: Treatment options for recurrent glioblastoma remain limited, with only modest activity of second line chemotherapy. Despite the absence of well controlled trials, bevacizumab is widely used for recurrent glioblastoma. Nonetheless, it remains unclear if the high response rates observed after treatment with bevacizumab translate into an overall survival (OS) benefit. We report the first randomized phase II trial on bevacizumab in recurrent glioblastoma with a control arm without bevacizumab. METHODS: This was multicenter phase II study conducted in 14 Dutch sites. Patients with a first recurrence of a glioblastoma after chemo-irradiation with temozolomide were randomized between treatment with oral lomustine 110 mg/m 2 once every 6 weeks, with bevacizumab 10 mg/kg once every 2 weeks intravenously or with the combination lomustine 110 mg/m 2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Response was assessed using the RANO criteria. Primary endpoint was OS at 9 months. A safety analysis was planned after the first ten patients completed two cycles of 6 weeks in the combination arm. RESULTS: 153 patients were randomized, of which 148 were eligible. After the safety analysis the lomustine dosage in the combination arm was reduced to 90 mg/m 2 because of thrombocytopenia, resulting in bevacizumab dose delays. After reduction the treatment in the combination arm was well tolerated. The percentage 9 month OS (95% confidence interval) was 43% (29, 57) in the lomustine arm, 38% (25, 51) in the bevacizumab arm, and 59% (43, 72) in the bevacizumab/lomustine 90 arm. Response rates were 35-40% for bevacizumab treated patients, and 5% in the lomustine single agent arm. CONCLUSION: This study does not show a meaningful OS at 9 months after treatment with bevacizumab alone. However, the results of combination therapy of bevacizumab with lomustine met the prespecified criterion for further phase III studies. AKNOWLEDGMENTS: This study was supported by an unrestricted grant from Roche Nederland bv.

EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma

“…No active combination partner for bevacizumab has been identified in the setting of progressive disease, albeit in uncontrolled or non-comparative trials, suggesting that bevacizumab monotherapy should be administered outside clinical trials. Preliminary data indicate that the combination of bevacizumab and CCNU may be superior to either agent alone, 53 suggesting that this combination warrants further exploration as planned in a phase III trial by the EORTC.…”

Bevacizumab and glioblastoma: Scientific review, newly reported updates, and ongoing controversies

“…60 In this study, patients in the combination arm had better outcomes than patients in either of the monotherapy arms, with the primary endpoint of 9-month OS rate of 38% versus 43% versus 59%, respectively. In addition, the median OS was 8 months versus 8 months versus 11 months, respectively, with an impressive improvement in the 6-month PFS rate at 18% versus 11% versus 41%, respectively.…”

“…32,[59][60][61][62][63][64][65][66][67][68] The randomized phase 2 GLARIUS trial compared bevacizumab, irinotecan, and radiotherapy versus standard temozolomide and radiation in patients with O 6 -methylguanine-methyltransferase (MGMT)-unmethylated, newly diagnosed glioblastoma. 59 This study found the combination of bevacizumab and irinotecan with radiotherapy to be more favorable than standard therapy, with the 6-month PFS rate reported at 79.5% versus 41.3%, and a mean PFS of 9.7 months versus 6 months, respectively.…”

Pharmacists Perspective on Management of GBM

“…A Dutch study explored combining bevacizumab with lomustine [29]. The BELOB study trial randomly assigned patients to bevacizumab, lomustine, or bevacizumab plus lomustine at first recurrence of GBM.…”