General Information

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

Avastin is specifically indicated for use in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer.

Avastin is supplied as an injection for intravenous administration. The recommended dose is 15 mg/kg intravenously every 3 weeks in combination with carboplatin and paclitaxel.

Clinical Results

FDA Approval

The FDA approval of Avastin as first-line treatment of patients with locally advanced, metastatic, or recurrent non–squamous NSCLC was based on a single, large, randomized, active-controlled, open-label, multicenter study. A total of 878 chemotherapy-naïve patients with locally advanced, metastatic or recurrent non–squamous NSCLC were randomized (1:1) to receive six 21-day cycles of paclitaxel (200 mg/m2) and carboplatin (AUC 6) with or without Avastin 15 mg/kg. After completing or discontinuing chemotherapy, patients randomized to receive Avastin continued to receive Avastin alone until disease progression or until unacceptable toxicity. OS was statistically significantly longer for patients receiving Avastin with paclitaxel and carboplatin compared with those receiving chemotherapy alone. Median OS was 12.3 months versus 10.3 months. Based on investigator assessment which was not independently verified, patients were reported to have longer PFS with Avastin with paclitaxel and carboplatin compared to chemotherapy alone.

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) is a humanized antibody to vascular endothelial growth factor (VEGF). It 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.