National Stroke Foundation

Avastin (bevacizumab)

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

Company:

Approval Status:

Approved November 2014

Specific Treatments:

stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer

General Information

Avastin (bevacizumab) is a vascular endothelial growth factor directed antibody.

Avastin is specifically indicated for the following:

for use in combination with carboplatin and paclitaxel, followed by Avastin as a single agent, for the treatment of patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection;

for use in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan, for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens; 

for use in combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by Avastin as a single agent, for the treatment of patients with platinum sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Avastin is supplied as an injection for intravenous administration. The recommended dose is as follows:

Treatment of Stage III or IV Disease Following Initial Surgical Resection:

The recommended dose is 15 mg/kg intravenously every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by Avastin 15 mg/kg every 3 weeks as a single agent, for a total of up to 22 cycles or until disease progression, whichever occurs earlier.

Treatment of Recurrent Disease:

Platinum Resistant:

The recommended dose is 10 mg/kg intravenously every 2 weeks in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan (every week). 
The recommended dose is 15 mg/kg intravenously every 3 weeks in combination with topotecan (every 3 weeks).

Platinum Sensitive:

The recommended dose is 15 mg/kg intravenously every 3 weeks, in combination with carboplatin and paclitaxel for 6 to 8 cycles, followed by Avastin 15 mg/kg every 3 weeks as a single agent until disease progression. 
The recommended dose is 15 mg/kg intravenously every 3 weeks, in combination with carboplatin and gemcitabine for 6 to 10 cycles, followed by Avastin 15 mg/kg every 3 weeks as a single agent until disease progression.

 

Clinical Results

FDA Approval

The FDA approval of Avastin was based on the following trials:

Study MO22224: a multicenter, open-label, randomized study comparing Avastin with chemotherapy versus chemotherapy alone in patients with platinum-resistant, recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer that recurred within <6 months from the most recent platinum-based therapy (N=361). Patients had received no more than 2 prior chemotherapy regimens. Patients received one of the following chemotherapy regimens at the discretion of the investigator: paclitaxel (80 mg/m2 on days 1, 8, 15 and 22 every 4 weeks; pegylated liposomal doxorubicin 40 mg/m2 on day 1 every 4 weeks; or topotecan 4 mg/m2 on days 1, 8 and 15 every 4 weeks or 1.25 mg/m2 on days 1-5 every 3 weeks). Patients were treated until disease progression, unacceptable toxicity, or withdrawal. Forty percent of patients on the chemotherapy alone arm received Avastin alone upon progression. The main outcome measure was investigator-assessed PFS. The addition of Avastin to chemotherapy demonstrated a statistically significant improvement in investigator-assessed PFS. The median PFS was 6.8 months for the Avastin/chemo arm and 3.4 months for the chemo monotherapy arm.

Study AVF4095g: a randomized, double-blind, placebo-controlled study studying Avastin with chemotherapy versus chemotherapy alone in the treatment of patients with platinum sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have not received prior chemotherapy in the recurrent setting or prior bevacizumab treatment (N=484). Patients were randomized (1:1) to receive Avastin (15 mg/kg day 1) or placebo every 3 weeks with carboplatin (AUC 4, day 1) and gemcitabine (1000 mg/m2 on days 1 and 8) a for 6 to 10 cycles followed by Avastin or placebo alone until disease progression or unacceptable toxicity. The main outcome measures was investigator-assessed PFS.  A statistically significant prolongation in PFS was demonstrated among patients receiving Avastin with chemotherapy compared to those receiving placebo with chemotherapy: median 12.4 months versus 8.4 months, respectively. 

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.