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Avastin (bevacizumab)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved May 2009

Specific Treatments:

recurrent glioblastoma in adults

Therapeutic Areas

General Information

Avastin is a vascular endothelial growth factor directed antibody. 

Avastin is specifically indicated for the treatment of recurrent glioblastoma in adults.

Avastin is supplied as an injection for intravenous administration. The recommended dose is 10 mg/kg intravenously every 2 weeks.
 

Clinical Results

FDA Approval

The FDA approval of Avastin for glioblastoma was based on a multicenter, randomized, open-label study in patients with recurrent GBM. Patients with first progression following radiotherapy and temozolomide were randomized (2:1) to receive Avastin (10 mg/kg every 2 weeks) with lomustine (90 mg/m2 every 6 weeks) or lomustine (110 mg/m2 every 6 weeks) alone until disease progression or unacceptable toxicity. Randomization was stratified by World Health Organization performance status (0 vs. >0), steroid use (yes vs. no), largest tumor diameter (≤ 40 vs. > 40 mm), and institution. The main outcome measure was OS. A total of 432 patients were randomized to receive lomustine alone (N=149) or Avastin with lomustine (N=283). No difference in OS was observed between arms; therefore, all secondary outcome measures are descriptive only. PFS was longer in the Avastin with lomustine arm with a median PFS of 4.2 months in the Avastin with lomustine arm and 1.5 months in the lomustine arm. Among the 50% of patients receiving corticosteroids at the time of randomization, a higher percentage of patients in the Avastin with lomustine arm discontinued corticosteroids (23% vs. 12%).

One single arm single center study and a randomized noncomparative multicenter study evaluated the efficacy and safety of Avastin 10 mg/kg every 2 weeks in patients with previously treated GBM. Response rates in both studies were evaluated based on modified WHO criteria that considered corticosteroid use. In study AVF3708g, the response rate was 25.9% with a median duration of response of 4.2 months. In Study NCI 06-C-0064E, the response rate was 19.6% with a median duration of response of 3.9 months.

Side Effects

Adverse effects associated with the use of Avastin may include, but are not limited to, the following:

epistaxis

headache,

hypertension

rhinitis

proteinuria

taste alteration

dry skin

rectal hemorrhage

lacrimation disorder

back pain

exfoliative dermatitis

The Avastin drug label comes with the following Black Box Warning: Gastrointestinal Perforations: The incidence of gastrointestinal perforation, some fatal, in patients receiving Avastin ranges from 0.3% to 3%. Discontinue Avastin in patients who develop gastrointestinal perforations. Surgery and Wound Healing Complications: The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in patients receiving Avastin. Discontinue Avastin in patients who develop wound healing complications that require medical intervention. Withhold Avastin at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery, and until the wound is fully healed. Hemorrhages: Severe or fatal hemorrhage, including hemoptysis, gastrointestinal bleeding, hematemesis, CNS hemorrhage, epistaxis, and vaginal bleeding occur up to 5-fold more frequently in patients receiving Avastin. Do not administer Avastin to patients with a recent history of hemoptysis. Discontinue in patients who develop Grade 3-4 hemorrhage.

Mechanism of Action

Avastin (bevacizumab) binds VEGF and prevents the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis.

Additional Information

For additional information regarding Avastin or recurrent glioblastoma, please visit https://www.avastin.com/

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