Bevacizumab and Temozolomide in First Recurrence of Glioma Without 1p/19q Codeletion
In a phase II trial funded by the European Organisation for Research and Treatment of Cancer and reported in The Lancet Oncology, van den Bent et al found no evidence of a survival benefit with the addition of bevacizumab (Avastin) to temozolomide in patients with a first recurrence of World Health Organization grade II or III glioma without the 1p/19q codeletion.
In the open-label trial, conducted at 32 European centers, 155 patients were randomized between February 2011 and July 2015 to receive either temozolomide at 150 to 200 mg/m² on days 1 to 5 every 4 weeks for a maximum of 12 cycles (n = 77) or the same temozolomide regimen plus bevacizumab at 10 mg/kg every 2 weeks until disease progression (n = 78). Previous chemotherapy must have been stopped at least 6 months before enrollment, and radiotherapy, at least 3 months before enrollment. Overall, 44% of patients in the combination group and 47% in the temozolomide group had grade III disease.
The primary endpoint was overall survival at 12 months in the per-protocol population, consisting of 69 patients in the combination group (7 ineligible, 2 did not start treatment) and 72 in the temozolomide group (3 ineligible, 2 did not start treatment).
Overall Survival and Adverse Events
Median follow-up was 28 months. In the per-protocol population, overall survival at 12 months was achieved by 38 (55%) of 69 patients in the combination group vs 44 (61%) of 72 in the temozolomide group. Median overall survival was 12.9 months vs 14.8 months. Median progression-free survival was 5.9 months vs 6.3 months.
Grade 3 or 4 hematologic toxicity occurred in 33% of the combination group vs 23% of the temozolomide group. The most common nonhematologic toxicities of any grade were nervous system disorders (86% vs 79%), fatigue (80% vs 70%), and nausea (56% vs 52%). Infections occurred in 38% vs 23% of patients. One treatment-related death occurred in the combination group due to infection after intratumoral hemorrhage during treatment-related grade 4 thrombocytopenia.
The investigators concluded, “We found no evidence of improved overall survival with bevacizumab and temozolomide combination treatment vs temozolomide monotherapy. The findings from this study provide no support for further phase III studies on the role of bevacizumab in this disease.”
Martin J. van den Bent, MD, of the Brain Tumor Center, Erasmus MC Cancer Institute, is the corresponding author for The Lancet Oncology article.
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