BEVACIZUMAB SLOWS PROGRESSION OF HIGH GRADE GLIOMA

David Muñoz Carmona

NEW YORK (Reuters Health) Apr 20 - The antiangiogenic agent bevacizumab (Avastin) appears to slow the progression of recurrent alkylator-refractory 1p19q codeleted anaplastic oligodendroglioma, according to a retrospective study published in the April 15 issue of Cancer.There is no standard therapy for this brain tumor, note authors Dr. Marc C. Chamberlain and Dr. Sandra Johnston at the Fred Hutchinson Cancer Center, Seattle.Their study involved 22 patients ages 24 to 60 years, for whom primary therapy included surgery, radiotherapy and adjuvant chemotherapy, followed by one salvage therapy.Upon second recurrence of the tumor, patients were treated with an intravenous infusion of bevacizumab 10 mg/kg administered every 14 days, with dexamethasone permitted for symptomatic control. Patients underwent a median of 14.5 cycles (range, 2-39).One patient demonstrated stable disease, 15 demonstrated a partial radiographic response, and 6 demonstrated progressive disease after 2 cycles.Median time to tumor progression was 6.75 months (range 1-18 months), and median overall survival was 8.5 months (range 3-19 months). Six- and 12-month progression-free survival rates were 68% and 23%, respectively.Toxicity was "modest," the authors note, with nine grade 3 adverse events during 391 treatment cycles, and no grade 4 or 5 adverse events.Drs. Chamberlain and Johnston comment that, "regarding the primary endpoint of 6-month progression-free survival, the results exceed the 20% threshold for success.... More problematic, however, is the lack of overall survival benefit with bevacizumab."In a prepared statement, Dr. Chamberlain notes that, "of all of the targeted therapies for gliomas, this has been the most promising. And this is practice changing."

Phase II Trial of Single-Agent Bevacizumab Followed by Bevacizumab Plus Irinotecan at Tumor Progression in Recurrent Glioblastoma

David Muñoz Carmona
Teri N. Kreisl, Lyndon Kim, Kraig Moore, Paul Duic, Cheryl Royce, Irene Stroud, Nancy Garren,Megan Mackey, John A. Butman, Kevin Camphausen, John Park, Paul S. Albert, and Howard A. Fine From the Neuro-Oncology Branch, Radiation Oncology Branch and BiometricBranch, National Cancer Institute; Surgical Neurology Branch, National Institutesof Neurological Disorders and Stroke; and the Department of Radiology,
the Clinical Center, National Institutes of Health, Bethesda, MD.Submitted January 25, 2008; accepted September 25, 2008; published online ahead of print at www.jco.org on December 29, 2008.
Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Clinical Trials repository link available on JCO.org.

A B S T R A C T
Purpose
To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma.
Patients and Methods
Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks.After tumor progression, patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m2 or 125 mg/m2 every 2 weeks, depending on use of enzyme-inducingantiepileptic drugs. Complete patient evaluations were repeated every 4 weeks.
Results
Forty-eight heavily pretreated patients were accrued to this study. Thromboembolic events
(12.5%), hypertension (12.5%), hypophosphatemia (6%), and thrombocytopenia (6%) were the most common drug-associated adverse events. Six patients (12.5%) were removed from study for drug-associated toxicity (five thromboembolic events, one bowel perforation). Thirty-four patients (71%) and 17 patients (35%) achieved radiographic response based on Levin and Macdonald criteria, respectively. Median progression-free survival (PFS) was 16 weeks (95% CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%). The 6-month overall survival was 57%(95% CI, 44% to 75%). Median overall survival was 31 weeks (95% CI, 21 to 54 weeks). Early magnetic resonance imaging response (first 96 hours and 4 weeks) was predictive of long-term PFS, with the Levin criteria being more predictive than Macdonald criteria. Of 19 patients treated with bevacizumab plus irinotecan at progression, there were no objective radiographic responses.
Eighteen patients (95%) experienced disease progression by the second cycle, and the median PFS was 30 days.
Conclusion
We conclude that single-agent bevacizumab has significant biologic and antiglioma activity in patients with recurrent glioblastoma.
J Clin Oncol 27:740-745. Published by the American Society of Clinical Oncology