What is the recommended use and dosage of Bevacizumab (bevacizumab) in cancer treatment?

Bevacizumab in Cancer Treatment: Recommended Use and Dosing

Bevacizumab is a humanized monoclonal antibody targeting VEGF that should be used in combination with chemotherapy for specific advanced cancers at doses ranging from 5-15 mg/kg IV every 2-3 weeks, depending on the cancer type and chemotherapy regimen. 1

Approved Indications and Dosing

Metastatic Colorectal Cancer (mCRC)

• 5 mg/kg IV every 2 weeks when combined with bolus-IFL or fluoropyrimidine-based chemotherapy 1
• 10 mg/kg IV every 2 weeks when combined with FOLFOX4 1
• 7.5 mg/kg IV every 3 weeks is an alternative dosing option with fluoropyrimidine-based regimens 1
• For second-line therapy after progression on first-line bevacizumab, use 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin chemotherapy 1
• Bevacizumab adds modest survival benefit in mCRC (HR 0.85; 95% CI 0.78-0.93), with benefit more evident in irinotecan-based regimens than oxaliplatin-based regimens 2

Non-Small Cell Lung Cancer (NSCLC)

• 15 mg/kg IV every 3 weeks in combination with carboplatin and paclitaxel for first-line treatment of non-squamous NSCLC 1
• Absolute contraindication: squamous cell histology due to risk of fatal hemoptysis 2
• Exclude patients with brain metastases, clinically significant hemoptysis, ECOG performance status >1, or therapeutic anticoagulation from initial therapy 2

Recurrent Glioblastoma

• 10 mg/kg IV every 2 weeks as monotherapy 1

Metastatic Renal Cell Carcinoma

• 10 mg/kg IV every 2 weeks in combination with interferon alfa 1

Cervical Cancer (Persistent, Recurrent, or Metastatic)

• 15 mg/kg IV every 3 weeks combined with paclitaxel and cisplatin, or with paclitaxel and topotecan 1

Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

• Platinum-resistant recurrent disease: 10 mg/kg IV every 2 weeks with paclitaxel, pegylated liposomal doxorubicin, or weekly topotecan 1
• Alternative: 15 mg/kg IV every 3 weeks with topotecan given every 3 weeks 1

Critical Safety Considerations and Contraindications

Surgical Timing (Mandatory)

• Withhold bevacizumab for at least 28 days before elective surgery 1
• Do not resume until at least 28 days after major surgery and adequate wound healing is confirmed 1
• The panel recommends at least 6 weeks (2 half-lives) between last bevacizumab dose and elective surgery 2
• Reinitiation should be delayed 6-8 weeks postoperatively 2

Absolute Contraindications Requiring Discontinuation

• Gastrointestinal perforation (any grade) 1
• Tracheoesophageal fistula (any grade) 1
• Grade 4 fistula or fistula involving internal organs 1
• Necrotizing fasciitis 1
• Grade 3 or 4 hemorrhage 1
• Recent hemoptysis ≥2.5 mL (½ teaspoon) 1
• Arterial thromboembolism (severe) 1
• Grade 4 venous thromboembolism 1
• Hypertensive crisis or hypertensive encephalopathy 1
• Posterior reversible encephalopathy syndrome (PRES) 1
• Nephrotic syndrome 1
• Severe infusion reactions 1
• Congestive heart failure 1

Relative Contraindications Requiring Withholding

• Uncontrolled severe hypertension (withhold until controlled with medical management) 1
• Proteinuria ≥2 grams per 24 hours without nephrotic syndrome (withhold until <2 grams per 24 hours) 1
• Wound healing complications (withhold until adequate healing; safety of resumption not established) 1

Special Populations and Situations

Brain Metastases

• Treated brain metastases are NOT a contraindication to bevacizumab therapy 2
• Patients must have previously treated brain metastases with no progression or hemorrhage at baseline 2
• In the PASSPORT trial, no grade 1-5 CNS hemorrhages occurred in 106 evaluable patients with treated brain metastases receiving bevacizumab 2
• Across multiple studies, only 3 of 2,897 patients (0.1%) with brain metastases developed cerebral hemorrhage while on bevacizumab 2

Therapeutic Anticoagulation

• Not an absolute contraindication based on current evidence 2
• In pooled analysis, severe bleeding risk was 4.1% in bevacizumab group versus 4.2% in control group among anticoagulated patients 2
• Monitor closely for bleeding complications 2

Perioperative Setting for Resectable Metastases

• The panel does NOT recommend bevacizumab in the perioperative stage IV setting 2
• This is based on lack of efficacy in adjuvant settings for stage II/III colon cancer 2

Continuation Beyond Progression

First-Line to Second-Line Transition

• Continuation of bevacizumab beyond progression is recommended when switching chemotherapy regimens 2
• The ML18147 trial demonstrated modest OS improvement (11.2 vs 9.8 months; HR 0.81; P=0.0062) with bevacizumab continuation 2
• The BEBYP trial showed PFS benefit (6.8 vs 5.0 months; HR 0.70; P=0.001) with bevacizumab continuation 2
• Bevacizumab is preferred over ziv-aflibercept and ramucirumab in second-line therapy based on toxicity and cost 2

No Rebound Effect

• No evidence of accelerated recurrence or increased mortality after bevacizumab discontinuation 2
• Meta-analysis of 4,205 patients found no difference in time to progression or mortality with bevacizumab discontinuation versus placebo 2

Combination Therapy Restrictions

Do NOT combine bevacizumab with anti-EGFR antibodies (cetuximab or panitumumab) 2

• Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended due to lack of benefit and increased toxicity 2

Pharmacokinetics and Dosing Adjustments

• Half-life: approximately 20 days 3
• Steady state reached in approximately 100 days 3
• No dose reductions recommended for bevacizumab 1
• No dosage adjustments required based on age, sex, or renal function 3
• Linear pharmacokinetics in the dose range of 0.3-10 mg/kg every 2-3 weeks 3

Common Pitfalls to Avoid

1. Do not use bevacizumab in squamous cell NSCLC due to fatal hemoptysis risk 2
2. Do not perform surgery within 28 days of last bevacizumab dose 1
3. Do not restart bevacizumab within 28 days after major surgery 1
4. Do not combine with anti-EGFR antibodies 2
5. Do not exclude patients with treated brain metastases from bevacizumab therapy 2
6. Do not discontinue bevacizumab at first progression when continuing to second-line chemotherapy 2