Yesterday,
the FDA granted bevacizumab accelerated approval for the
treatment of relapsed glioblastoma.
On March 31, the FDA Oncologic Drugs Advisory Committee
voted unanimously
to
recommend the drug for accelerated approval. This designation allows
provisional approval of drugs that treat serious disease or that fill an unmet
medical need based on a surrogate endpoint.
The approval was based on data from two phase-2 studies
that showed an improvement in objective response rate. There are currently no
data available from randomized, controlled trials showing an improvement in
disease-related symptoms or increased survival from the drug.
Data from both studies were positive and independently
reviewed, but neither trial was comparative.
The application was based on data from the
AVF3708g study, an open-label, multicenter study, which
included 167 patients. Researchers randomly assigned patients with glioblastoma
previously treated with temozolomide (Temodar, Schering) and radiation to
either bevacizumab (Avastin, Genentech) alone (n=85) or in combination with
irinotecan (n=82).
The committee recommended accelerated approval based on
data from the single-agent arm of this study.
According to data submitted to the FDA, 26% of patients
assigned to bevacizumab had an objective response (95% CI, 17%-36.1%);
six-month PFS was 42.6% (95% CI, 31.3-53.9). The median PFS was 4.2 months (95%
CI, 3.0-5.7).
The second study was a single-arm study of the drug.
Fifty-six patients were treated with bevacizumab alone. Twenty percent of
patients responded to the drug (95% CI, 10.9%-31.3%). Median duration of
response was 3.9 months (95% CI, 2.4-17.4).
The most common grade-3 or higher adverse effects were
high blood pressure and seizures. Two deaths possibly associated with adverse
events occurred in patients treated with bevacizumab alone.
Bevacizumab is already approved to treat colorectal,
lung and breast cancer. – by Leah Lawrence
This is a great advance for our patients with glioblastoma because
bevacizumab is really the first drug that has shown a clear cut improvement in
quality of life for these patients. I am very encouraged that it will now be
available to patients across the country who have recurrent glioblastoma. It is
also well timed because there is a lot of experience with this drug in other
malignancies and unfortunately, we do not have other drugs that have been
effective for patients who have recurrent glioblastoma. The FDA has done the
right thing giving this drug accelerated approval. Finally, although this is a
very exciting development and it gives us all encouragement in treating our
patients, I would still urge physicians to offer clinical trials to patients
with this disease because we still have a lot of work to do.
– David M. Peerebom, MD
Associate Professor at the Cleveland Clinic Lerner College
of Medicine