What are the contraindications for Avastin (bevacizumab) in patients with a history of cancer?

Avastin (Bevacizumab) Contraindications

Avastin has no absolute contraindications listed in the FDA label, but there are critical clinical situations where the drug must be avoided or discontinued to prevent life-threatening complications. 1

Critical Exclusion Criteria (Avoid Bevacizumab)

Hemorrhage Risk

• Do not use in patients with recent hemoptysis (≥2.5 mL of red blood), particularly in lung cancer patients, as fatal pulmonary hemorrhage occurred in 2.3% of bevacizumab-treated patients versus 0.5% with chemotherapy alone 2
• Permanently discontinue for Grade 4 hemorrhage 3
• The initial ECOG 4599 trial excluded patients with hemoptysis after 5 deaths from catastrophic hemoptysis occurred in a phase 2 study, primarily in squamous histology patients 4

Surgical Considerations

• Discontinue bevacizumab at least 6 weeks before any elective surgery due to severe wound healing complications 5
• Do not reinitiate until at least 6-8 weeks postoperatively 5
• When bevacizumab was stopped ≥6 weeks before surgery, wound healing complications dropped to 1.3% versus 13% when this interval was not observed 5

Gastrointestinal Perforation Risk

• Avoid in patients with extensive prior intra-abdominal surgery due to increased risk of gastrointestinal perforation 5
• Fatal gastrointestinal perforation has been reported in clinical trials 2, 6

Cardiovascular Contraindications

• Do not use with anthracycline-based chemotherapy - bevacizumab is specifically not indicated for this combination 1
• Discontinue permanently in patients who develop congestive heart failure 1
• The rate of CHF was 4% in patients receiving bevacizumab with prior anthracycline treatment versus 0.6% with chemotherapy alone 1

Historical Exclusion Criteria (Now Reconsidered)

Brain Metastases

• Previously treated brain metastases are no longer an absolute contraindication based on the PASSPORT study 4
• Patients must have no evidence of progression or hemorrhage at baseline on brain imaging within 1 week of treatment 4
• At least 3 months must have elapsed since neurosurgery 4
• The PASSPORT study found no Grade 1-5 CNS hemorrhages in 106 evaluable patients with treated brain metastases 4
• The ATLAS study authors specifically stated that patients with treated CNS metastases should not be excluded from bevacizumab therapy 4

Anticoagulation

• Full-dose anticoagulation is no longer an absolute contraindication 4
• In the PASSPORT study, 17% of patients were on anticoagulants for >1 week (9% on enoxaparin, 7% on warfarin, 10% on daily aspirin) with acceptable safety 4
• However, avoid combining bevacizumab with antiplatelet therapy in ESRD patients without compelling indication due to substantially elevated bleeding risk 3

Squamous Histology in NSCLC

• Squamous or predominantly squamous NSCLC remains a relative contraindication due to life-threatening hemoptysis in 4 of 13 patients with squamous histology in a phase 2 study 2
• The pivotal ECOG 4599 trial specifically excluded patients with primarily squamous histology 4

Additional Safety Considerations

Arterial Thromboembolic Events

• Increased risk in patients aged ≥65 years, particularly stroke and other arterial events 4
• Fatal arterial thromboembolic events including CNS infarction and myocardial infarction have been reported 2

Renal Impairment

• Standard dosing does not require adjustment for renal impairment, but bevacizumab's nephrotoxic effects must be considered 3
• Monitor for proteinuria and nephrotic syndrome 2

Pregnancy and Fertility

• Inform females of reproductive potential of the risk of ovarian failure prior to initiating bevacizumab 1
• Long-term effects on fertility are unknown 1

Common Pitfalls to Avoid

• Do not continue bevacizumab beyond progression - there are insufficient data to support continuation with second-line regimens after progression on a bevacizumab-containing first-line regimen 4
• Do not combine bevacizumab with anti-EGFR antibodies (cetuximab or panitumumab) - combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended 4
• Do not ignore the 6-week surgical window - calculate backward from the surgical date to determine optimal timing of bevacizumab doses 5