By Cameron Johnston
CHICAGO -- June 5, 2008 -- Glioblastoma multiforme, also known as grade IV astrocytoma, accounts for more than 60% of all brain cancers in patients over the age of 50 years and has a particularly poor prognosis, with a high rate of recurrence, and response rates ranging from 0% to 15%.
In an oral presentation at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting this year, Timothy Cloughesy, MD, Neuro-Oncology Program, University of California at Los Angeles, Los Angeles, California presented data from a phase 2 randomised, noncomparative study comparing the use of bevacizumab alone or with irinotecan (CPT-11) in the treatment of this disease.
In a presentation on May 31, Dr. Cloughesy said that prior to the introduction of temozolomide for the treatment of brain cancers, there were no standard treatments and patients progressed from surgery to radiation therapy to palliative care and death in fairly short order.
Prior to the introduction of temozolomide, the 6-month progression-free survival (PFS) was in the order of 15 weeks, and median survival was around 25 weeks. Since temozolomide-containing regimens were introduced, the 6-month PFS has improved to around 28 weeks and median survival has improved to 40 weeks.
However, the prognosis still is not encouraging, and relapses are frequent. The question then, is how to treat patients who have relapsed or had recurrences following treatment with a temozolomide-containing regimen.
In their study, Dr. Cloughesy and colleagues randomised 85 patients who received bevacizumab as a single agent and 82 who received bevacizumab plus irinotecan. The dose of irinotecan depended on whether the patient was taking anticonvulsant therapy. Patients who progressed in the bevacizumab arm were allowed to begin using irinotecan as well.
The primary endpoint of the study was 6-month PFS and objective response rates between the 2 arms. Data for overall survival was cut off at November 2007, while data for toxicities, 6-month PFS, and objective response rates were cut off in September 2007.
Patients were evenly matched for demographic and disease characteristics.
Duration of treatment was 16 weeks in the bevacizumab-alone arm and 22 weeks in the bevacizumab/irinotecan arm. Overall survival rates were 9.2 months and 8.7 months, respectively, while 6-month PFS was 42.6% and 50.3%, respectively. An objective response was seen in 28% of patients receiving bevacizumab alone and 38% of those receiving the dual therapy.
There were few safety issues observed with these treatments. Side effects traditionally associated with the use of bevacizumab -- including infections, venous-thromboembolic events, and wound healing complications -- were relatively infrequent, occurring in 9.5%, 2.4%, and 3.6% of patients, respectively. However, each of these adverse events was seen more frequently in the group receiving dual bevacizumab/CPT-11 compared with the arm receiving bevacizumab alone.
These data demonstrate that bevacizumab, either alone or in combination with CPT-11, can have significant activity in this group of patients with poor prognosis, Dr. Coughesy and colleagues concluded. It was also encouraging to note that patients who were taking corticosteroids at enrolment were able to reduce their use of these drugs.
Further studies are planned to evaluate the use of bevacizumab and other combination therapies in the treatment of this devastating form of brain cancer.
Funding for this study was provided in part by Genentech, Inc.
[Presentation title: A Phase II, Randomized, Non-Comparative Clinical Trial of the Effect of Bevacizumab (BV) Alone or in Combination With Irinotecan (CPT) on 6-Month Progression Free Survival (PFS6) in Recurrent, Treatment-Refractory Glioblastoma (GBM). Abstract 2010b]
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