A disappointing showing of a phase 3 study found that Avastin (bevacizumab) in newly diagnosed glioblastoma did not prolong survival. The study was presented as one of the headlining studies in the Plenary session at the annual meeting on Sunday.
Glioblastoma is an aggressive, hard-to-treat brain tumor that affects about 10,000 people at year in the U.S. Average survival for this type of brain tumor is fewer than 18 months, and is treated with a variety of radiation, surgery and chemotherapy, including temozolomide.
Avastin was granted accelerated approval for treatment of recurrent glioblastoma in 2009 due to promising phase 2 studies that showed the drug delayed disease progression. This makes sense because the tumor is highly vascular, sending out proteins to encourage blood vessel growth to the tumor to help grow–a process called angiogenesis. Avastin, which blocks the pathway involving this protein, called vascular endothelial growth factor, would be a logical choice to treat newly diagnosed glioblastoma. The thought was the earlier you treat this tumor with an anti-angiogenic therapy, the less lethal it would be.
With that in mind, the drug is sometimes used to treat newly diagnosed patients in the hopes that the same effect seen in recurrent glioblastoma would apply to this patient population.
Unfortunately, that’s not the case. This latest large-scale phase 3 study, which was to confirm the effectiveness of Avastin and possibly improve survival, actually found that the drug conveyed no benefit. Survival was 16.1 months in the placebo arm and 15.7 months in the Avastin arm. Progression-free survival was 7.3 months and 10.7 months, respectively. Although the trend was toward Avastin, the difference could be just due to chance (not statistically significant.) Patients who were randomized to receive Avastin also had more side effects, including low platelet counts, which can contribute to bleeding problems, as well as blood clots and high blood pressure.
The study was designed to look for overall survival and progression-free survival at the same time, which was interesting (usually it’s one or the other). The researchers required tumor tissue samples to provide molecular testing, which will be helpful in the long run, because they are looking for any sign that Avastin may work in a certain group of patients. They also recorded patient outcomes, symptom burden, quality of life and cognitive function.
How do these results compare to another phase 3 study in newly diagnosed glioblastoma patients? The AVAglio trial data released last year found that the addition of Avastin to temozolomide and radiation delayed progression-free survival, but no difference in overall survival has been seen yet. There are slight differences in the trial, so researchers are watching the two studies closely to gain additional insight and data on different subsets of patients.
Unfortunately, the past few phase 3 studies in brain cancer have all been disappointing, ranging from the Avastin trial to cilengitide to cediranib.
It’s important to note that these results do not affect the use of Avastin in recurrent glioblastoma.