Dutch Phase II Study Supports Phase III Evaluation of Bevacizumab Plus Lomustine, but Not Bevacizumab Alone, in Recurrent Glioblastoma
Bevacizumab (Avastin) is frequently used in patients with recurrent glioblastoma, although it is unclear whether responses observed with such treatment result in improved overall survival. In the phase II Dutch BELOB study reported in The Lancet Oncology, Taal et al found that overall survival results supported phase III evaluation of the combination of bevacizumab and lomustine (CeeNU) but not bevacizumab monotherapy.
Study Details
In this open-label trial, 153 adult patients from 14 Dutch hospitals with a first recurrence of glioblastoma after temozolomide chemoradiotherapy were randomly assigned between December 2009 and November 2011 to receive oral lomustine at 110 mg/m2 once every 6 weeks, intravenous bevacizumab at 10 mg/kg once every 2 weeks, or combination treatment at the same doses. The primary endpoint outcome was overall survival at 9 months in the intent-to-treat population.
A preplanned safety analysis after eight patients had received the combination regimen showed that three had grade 3 and two had grade 4 thrombocytopenia, with these toxicities requiring a reduction in bevacizumab dose intensity. The lomustine dose in the combination group was subsequently reduced to 90 mg/m2. In addition to the eight combination recipients getting the higher lomustine dose, 51 received bevacizumab alone, 47 received lomustine alone, and 47 received bevacizumab plus lomustine at 90 mg/m2.
9-Month Overall Survival
The 9-month overall survival rate was 43% (95% confidence interval [CI] = 29%–57%) in the lomustine group, 38% (95% CI = 25%–51%) in the bevacizumab group, 59% (95% CI = 43%–72%) in the bevacizumab/lomustine 90 mg/m2 group, 87% (95% CI = 39%–98%) in the bevacizumab/lomustine 110 mg/m2 group, and 63% (95% CI = 49%–75%) in the two bevacizumab/lomustine groups combined.
Toxicity
Combination treatment was well tolerated after the lomustine dose reduction. The most common grade 3 or higher adverse events were hypertension, which occurred in 26% of the bevacizumab group, 7% of the lomustine group, and 25% of the bevacizumab/lomustine 90 mg/m2 group, fatigue (4%, 9%, and 18%), and infection (6%, 4%, and 11%).
The investigators concluded, “The combination of bevacizumab and lomustine met prespecified criteria for assessment of this treatment in further phase 3 studies. However, the results in the bevacizumab alone group do not justify further studies of this treatment.”
Martin J. van den Bent, MD, of Erasmus MC Cancer Center, Rotterdam, is the corresponding author for The Lancet Oncology article.
The study was funded by Roche Nederland and KWF Kankerbestrijding. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
