What are the contraindications for Bevacizumab (Avastin) therapy?

Contraindications of Bevacizumab

Bevacizumab has no absolute contraindications listed in formal guidelines, but several high-risk clinical scenarios represent relative contraindications where the drug should be avoided or used with extreme caution due to unacceptable mortality and morbidity risks. 1

High-Risk Clinical Scenarios (Relative Contraindications)

Perioperative Period

• Stop bevacizumab at least 6 weeks before any elective surgery to minimize wound healing complications, which occur at significantly higher rates (13% vs 3.4% with chemotherapy alone) when surgery occurs during active treatment 1
• Do not restart bevacizumab until 6-8 weeks postoperatively to allow adequate wound healing—waiting only 4 weeks is insufficient 1, 2
• When bevacizumab is stopped ≥6 weeks before surgery, wound complication rates drop to acceptably low levels (1.3% vs 0.5%) 1
• The NCCN does not recommend bevacizumab in the perioperative stage IV setting for resectable metastases due to lack of efficacy data 1

Extensive Prior Intra-Abdominal Surgery

• Patients with extensive peritoneal stripping or peritoneal debulking surgery represent a major risk factor for gastrointestinal perforation and warrant extreme caution 1
• Patients with advanced ovarian cancer who underwent peritoneal debulking had unacceptably high perforation rates with bevacizumab 1
• Gastrointestinal perforation is rare but potentially fatal, accounting for 7.1% of treatment-related deaths 1, 3
• The actual risk factor is peritoneal debulking surgery itself, not the presence of an intact primary tumor 1

Active or Recent Bleeding/Hemorrhage Risk

• Hemorrhage accounts for 23.5% of bevacizumab-related treatment deaths 1
• Serious bleeding events including gastrointestinal hemorrhage (2.7%) and cerebral hemorrhage (2.6%) are well-documented 3
• Patients with conditions predisposing to bleeding or those on anticoagulants require careful risk-benefit assessment 4

Arterial Thromboembolic Disease

• The risk of arterial thromboembolic events is particularly elevated in patients ≥65 years of age 1
• The overall incidence of arterial thromboembolic events is significantly increased with bevacizumab 1
• Thromboembolic events account for 4.0% of serious adverse reactions, with pulmonary embolism at 3.2% 3
• Bevacizumab should be discontinued for new life-threatening venous or arterial thromboembolism 2

Serious Adverse Events Requiring Discontinuation

Gastrointestinal Perforation

• Incidence reported as high as 4.8% in pharmacovigilance data 3
• Bevacizumab must be discontinued permanently in patients who experience gastrointestinal perforation 2
• Monitor closely for abdominal pain, constipation, and signs of peritonitis throughout therapy 2

Necrotizing Fasciitis

• Can occur fatally with bevacizumab, usually secondary to wound healing complications, GI perforation, or fistula formation 1
• Despite being listed as rare in drug specifications, it shows high signal correlation in real-world data (PRR = 20.261) 5

Severe Proteinuria

• Monitor for proteinuria every 3-4 weeks throughout therapy 2
• Discontinue bevacizumab with persistent proteinuria of >2+ 2

Hypertensive Complications

• Hypertension is the most common adverse event with bevacizumab 2
• Hypertensive encephalopathy, though rare in specifications, shows high signal in real-world data (PRR = 18.288) 5
• Blood pressure should be routinely monitored and medically managed with antihypertensives as appropriate 2

Special Monitoring Considerations

Increased Treatment-Related Mortality

• Adding bevacizumab to chemotherapy increases treatment-related mortality (RR 1.33; 95% CI 1.02-1.73) 1
• In 18 cases of death directly caused by adverse reactions, 50% occurred after only one cycle 3

Rare but High-Signal Events

• Nasal septum perforation shows very high signal correlation (PRR = 47.502) despite being listed as rare 5
• Reversible posterior leukoencephalopathy syndrome can occur and requires monitoring 2
• Anastomotic complications (PRR = 457) and fistula formation are significant risks 5

Common Pitfalls to Avoid

• Do not assume intact primary tumor increases perforation risk—peritoneal debulking is the actual risk factor 1
• Do not restart bevacizumab earlier than 6-8 weeks postoperatively 1
• Do not overlook the increased mortality risk when counseling patients 1
• Do not fail to monitor blood pressure routinely, as hypertension is extremely common 2