van den Bent MJ, et al. - The use of bevacizumab in patients with first recurrence of grade II or III glioma who did not have 1p/19q co-deletion was assessed. Patients received temozolomide (150–200 mg/m², orally) monotherapy on days 1–5 every 4 weeks for a maximum of 12 cycles, or the same temozolomide regimen in combination with bevacizumab (10 mg/kg, intravenously) every 2 weeks until progression. As per outcomes, bevacizumab and temozolomide combination treatment resulted in no greater survival vs temozolomide monotherapy. Findings do not support further phase 3 studies on the role of bevacizumab in this disease.

Methods

• Researchers performed a randomized, open-label phase 2 trial, the TAVAREC trial, at 32 centers across Europe; patients with locally diagnosed grade II or III glioma without 1p/19q co-deletion, with a first and contrast-enhancing recurrence after initial radiotherapy or chemotherapy or both were enrolled.
• At least 6 months before enrolment, previous chemotherapy must have been stopped and at least 3 months before enrollment, radiotherapy must have been stopped.
• They randomly assigned the patients to groups electronically through the European Organization for Research and Treatment of Cancer web-based system; stratification was done by a minimization procedure using institution, initial histology (WHO grade II vs III), WHO performance status (0 or 1 vs 2), and previous treatment (radiotherapy, chemotherapy, or both).
• Temozolomide (150–200 mg/m², orally) monotherapy on days 1–5 every 4 weeks for a maximum of 12 cycles, or the same temozolomide regimen in combination with bevacizumab (10 mg/kg, intravenously) every 2 weeks was administered to patients until progression.
• Overall survival at 12 months in the per-protocol population was assessed as the primary endpoint.
• All patients who started their allocated treatment were analyzed for safety.

Results

• Researchers enrolled 155 patients and assigned them randomly to receive either monotherapy (n=77) or combination therapy (n=78) from February 8, 2011 to July 31, 2015.
• In the per-protocol population at 12 months, overall survival was achieved by 44 (61% [80% CI 53–69]) of 72 patients in the temozolomide group and 38 (55% [47–69]) of 69 in the combination group.
• They most frequently encountered hematological toxicity: in 17 (23%) of 75 patients in the monotherapy group and in 25 (33%) of 76 in the combination group developed grade 3 or 4 hematological toxicity.
• Other than hematological toxicities, nervous system disorders (59 [79%] of 75 patients in the monotherapy group vs 65 [86%] of 76 in the combination group), fatigue (53 [70%] vs 61 [80%]), and nausea (39 [52%] vs 43 [56%]) were the most common adverse events.
• The combination group had infections more frequently (29 [38%] of 76 patients) than the monotherapy group (17 [23%] of 75).
• In the combination group, 1 treatment-related death was reported (infection after intertumoral hemorrhage during a treatment-related grade 4 thrombocytopenia).

• Hypertension and hyponatremia were documented as the most common grade 3 or higher adverse events in the anlotinib arm.