What is Avastin (bevacizumab) used for and how does it work in cancer treatment?

What is Avastin (Bevacizumab)?

Avastin (bevacizumab) is a recombinant humanized monoclonal antibody that blocks vascular endothelial growth factor (VEGF) to inhibit tumor blood vessel formation, and it is FDA-approved for treating multiple cancers including metastatic colorectal cancer, non-squamous non-small cell lung cancer, recurrent glioblastoma, metastatic renal cell carcinoma, cervical cancer, and certain ovarian cancers. 1

Mechanism of Action

Bevacizumab works by binding to and neutralizing all active forms of VEGF-A, a protein that tumors use to stimulate new blood vessel growth 2, 3. By blocking VEGF:

• Inhibits new blood vessel formation (angiogenesis) that tumors require for growth and metastasis 4, 2
• Promotes regression of existing tumor microvessels and induces "normalization" of surviving mature vasculature 3
• Stabilizes vessels and prevents leakage from abnormal tumor blood vessels 3

The molecular weight is 149 kDa with an estimated half-life of approximately 20 days, reaching steady state in about 100 days 2, 3.

FDA-Approved Cancer Indications

Metastatic Colorectal Cancer

• First- or second-line treatment combined with fluorouracil-based chemotherapy 1
• Second-line treatment after progression on a first-line bevacizumab-containing regimen, combined with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin chemotherapy 1
• NOT indicated for adjuvant treatment of colon cancer 1

Non-Small Cell Lung Cancer

• First-line treatment for unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC combined with carboplatin and paclitaxel at 15 mg/kg every 3 weeks 1
• Squamous cell histology is excluded due to severe hemoptysis risk 5, 4

Other Approved Cancers

• Recurrent glioblastoma in adults: 10 mg/kg every 2 weeks 1
• Metastatic renal cell carcinoma: 10 mg/kg every 2 weeks combined with interferon alfa 5, 1
• Persistent, recurrent, or metastatic cervical cancer: 15 mg/kg every 3 weeks with paclitaxel and cisplatin or topotecan 1
• Platinum-resistant recurrent ovarian, fallopian tube, or primary peritoneal cancer: Various dosing with paclitaxel, pegylated liposomal doxorubicin, or topotecan 1

Clinical Efficacy Evidence

Colorectal Cancer

The addition of bevacizumab to chemotherapy provides modest but meaningful survival benefits 5:

• Median overall survival improvement: 4.7 months in first-line therapy 6, 7
• Progression-free survival advantage: HR 0.72 (95% CI, 0.66-0.78; P<0.00001) 5
• Overall survival advantage: HR 0.84 (95% CI, 0.77-0.91; P<0.00001) 5
• Benefit appears more pronounced with irinotecan-based regimens compared to oxaliplatin-based regimens 5

Lung Cancer

In non-squamous NSCLC, bevacizumab combined with carboplatin/paclitaxel demonstrated higher response rates, longer progression-free survival, and increased overall survival compared to chemotherapy alone 4.

Renal Cell Carcinoma

Bevacizumab combined with interferon alfa significantly prolonged progression-free survival (10.2 vs 5.4 months) and improved objective response rates (30.6% vs 12.4%) compared to interferon alone 5.

Critical Safety Considerations and Contraindications

Absolute Contraindications

• Recent hemoptysis: Do not administer to patients with recent hemoptysis 1
• Grade 4 hemorrhage: Permanently discontinue 8, 1
• Gastrointestinal perforation: Discontinue immediately 1

Surgical Timing Requirements

• Withhold at least 28 days (6-8 weeks preferred) before elective surgery due to wound healing complications 5, 8, 1
• Do not administer for at least 28 days after major surgery and until adequate wound healing 1
• The interval corresponds to approximately 2 half-lives of the drug 5

High-Risk Populations

• Patients ≥65 years: Increased risk of arterial thromboembolic events, particularly stroke 5, 8
• Extensive prior intra-abdominal surgery: Increased gastrointestinal perforation risk 5, 8
• Peritoneal debulking surgery: May predispose to gastrointestinal perforation 5

Previously Treated Brain Metastases

Brain metastases are no longer an absolute contraindication based on updated evidence 5, 8:

• Patients with treated brain metastases had acceptable safety profiles in multiple studies 5
• Must have no evidence of progression or hemorrhage on baseline brain imaging within 1 week of treatment 8
• At least 3 months must elapse since neurosurgery 8
• CNS bleeding risk was not significantly elevated (3.3% in bevacizumab group vs 1% in control) 5

Common Adverse Events

Treatment-related mortality is increased compared to chemotherapy alone (RR 1.33; 95% CI, 1.02-1.73; P=0.04) 5, with the most common fatal causes being:

• Hemorrhage (23.5% of fatalities) 5
• Neutropenia (12.2% of fatalities) 5
• Gastrointestinal perforation (7.1% of fatalities) 5

Other significant toxicities include hypertension, proteinuria, thromboembolic events, and necrotizing fasciitis 5, 1.

Important Treatment Limitations

• Do not continue bevacizumab beyond progression: Insufficient data support continuation with second-line regimens after progression on bevacizumab-containing first-line therapy 8
• Do not combine with anti-EGFR antibodies (cetuximab or panitumumab): Triple combination with cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended 8
• Monitor blood pressure: Treat hypertension and withhold if not medically controlled; discontinue for hypertensive crisis 1