One of the toughest cancers to treat effectively is glioblastoma multiforme (GBM), the most common form of primary brain cancer. Patients who have a recurrence of this cancer have had no effective therapy — until now. Researchers at the University of Virginia and several other leading brain tumor centers nationwide have discovered that a compound has shown the ability to effectively treat GBM in some patients.
Vascular endothelial growth factor (VEGF) has an important biologic role in this disease in fostering tumor growth by facilitating the growth of new blood vessels to feed the tumor. According to earlier studies, bevacizumab (BV), a humanized monoclonal antibody that specifically targets VEGF, in combination with irinotecan (also called CPT-11) could have a role in recurrent glioblastoma multiforme. The researchers set out to determine the clinical benefit of BV, both alone and in combination with CPT-11, in a multicenter, randomized phase II trial.
The results, presented in late 2007 at the 12 th annual Society for Neuro-Oncology meeting, were indeed promising for such an intractable disease. Study results substantially exceeded the pre-specified thresholds set for this work.
The primary endpoints were 6-month progression-free survival (PFS) defined as no clinical or MRI tumor growth and the objective response rate (ORR), which measures tumor shrinkage. Secondary endpoints included safety and survival. Response assessments were conducted by a blinded (without access to data on who took which drug(s)) and independent radiographic facility. All patients were followed for 24 weeks to determine efficacy and safety.
Evaluators at this independent facility assessing found that, when taking BV, 35.6 percent of patients on average had a 6-month survival with no progression of their cancer, and an objective response rate of 21.2 percent on average.
The combination of BV and CPT was even more effective, with results of 51 percent and 34.1 percent, respectively.
“Bevacizumab, taken alone or in combination with irinotecan, is well tolerated by most patients,” said Dr. David Schiff, co- director of the UVA Neuro-Oncology Program. “The drug is active in recurrent glioblastoma multiforme that has failed to respond to any prior therapy.”
The investigator group found similar results when they evaluated the patients. Those results showed that 44.7 percent of patients on average had a 6-month survival with no progression of their cancer, and an objective response rate of 38.8 percent on average. The combination therapy yielded results of 60.9 percent and 46.3 percent, respectively.
Patients on the study are still being treated and followed so that longer-term results will become available.
Known also by its brand name, Avastin, bevacizumab has already been approved for the treatment of metastatic colon cancer and most forms of metastatic non-small cell lung cancer.
In addition, UVA is planning and conducting additional brain tumor clinical trials with bevacizumab and other anti-VEGF agents.