Phase II trial of bevacizumab and temozolomide for upfront treatment of elderly patients with newly diagnosed glioblastoma.

2012 Background: Randomized clinical trials in newly diagnosed, elderly GBM patients have shown that treatment with temozolomide chemotherapy is at least equivalent to treatment with radiotherapy. Glioblastoma in elderly patients may also have high angiogenic activities. Bevacizumab is an antiangiogenic agent, a humanized monoclonal antibody directed against the vascular endothelial growth factor. We conduct a clinical trial of temozolomide and bevacizumab to evaluate the safety and efficacy of this combination in the treatment of elderly patients with newly diagnosed GBM, good performance status, and willing to forgo upfront treatment with radiation therapy. Methods: This is a phase II trial of newly diagnosed GBM patients age ≥70 with no prior treatments other than surgery and Karnofsky Performance Status (KPS) ≥60. Patients receive treatments 4-6 weeks after surgery with bevacizumab (10mg/kg every 2 weeks) and temozolomide (150-200 mg/m 2 for 5 days out of 28 days, up to 12 cycles) until tumor progression. Primary outcome measures are overall survival and safety evaluations. Results: From June 2010 to January 2016, 50 GBM patients enrolled in this study. To date, all patients have tumor progression and 3 are still alive. The median age is 75 (range 70 - 87), and median KPS is 80 (range 60-100). 15 patients have a gross total resection. 26 out of 49 patients with tissues available for evaluation have methylation of the MGMT promoter, and no patient has IDH-1 mutation. Median overall survival is 12.3 months (14.8 months for those with methylation of MGMT, 10.0 months for unmethylated MGMT). Serious adverse events related to treatments include wound healing problems (2), CNS hemorrhage (3), pulmonary embolism (4), and bowel perforation (1). Serious hematological adverse events include thrombocytopenia (3) and neutropenia (5). Conclusions: For patients with newly diagnosed GBM age ≥70, KPS ≥60, treatment with temozolomide and bevacizumab may show promising survival benefits and have tolerable side effects. More detailed safety and efficacy analysis will be presented. Clinical trial information: NCT01149850.