Bevacizumab is a vascular endothelial growth factor (VEGF) inhibitor that prevents angiogenesis and is indicated for the treatment of:

• Metastatic colorectal cancer in combination with intravenous 5-fluorouracil-based chemotherapy as first- or second-line therapy.
• Metastatic colorectal cancer with fluoropyrimidine–irinotecan or fluoropyrimidine–oxaliplatin regimens as second-line treatment in patients previously treated with a Bevacizumab-containing regimen.
• Non-squamous non-small cell lung cancer in combination with carboplatin and paclitaxel for first-line treatment of unresectable, locally advanced, recurrent, or metastatic disease.
• Glioblastoma as a single agent in adult patients with progressive disease following prior therapy. Clinical benefit is based on improvement in response rate; no proven benefit on survival or disease-related symptoms.
• Metastatic renal cell carcinoma in combination with interferon alfa.
• Cervical cancer in combination with paclitaxel and cisplatin or paclitaxel and topotecan for persistent, recurrent, or metastatic disease.
• Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer:
  (1) Platinum-resistant: in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan.
  (2) Platinum-sensitive: in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by Bevacizumab as a single agent.

Limitation of Use: Bevacizumab is not indicated for adjuvant treatment of colon cancer.

Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that binds to vascular endothelial growth factor (VEGF) and inhibits its biological activity in both laboratory and living systems. It consists of human framework regions combined with antigen-binding regions derived from a murine antibody that specifically targets VEGF. It has an approximate molecular weight of 149 kDa and is produced in mammalian (Chinese Hamster Ovary) cells in a nutrient medium containing gentamicin, which is not detectable in the final product. The drug appears as a clear to slightly opalescent, colorless to pale brown sterile solution with a pH of 6.2 for intravenous administration.

Patients should continue treatment until disease progression or unacceptable toxicity.

Metastatic Colorectal Cancer (mCRC): The recommended doses are 5 mg/kg or 10 mg/kg every 2 weeks when used in combination with intravenous 5-FU-based chemotherapy.

• Administer 5 mg/kg when used in combination with bolus-IFL.
• Administer 10 mg/kg when used in combination with FOLFOX4.
• Administer 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks when used in combination with a fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy regimen in patients who have progressed on a first-line Bevacizumab-containing regimen.

Non-Squamous Non-Small Cell Lung Cancer: (NSNSCLC): The recommended dose is 15 mg/kg every 3 weeks in combination with carboplatin and paclitaxel.

Glioblastoma: The recommended dose is 10 mg/kg every 2 weeks.

Metastatic Renal Cell Carcinoma (mRCC): The recommended dose is 10 mg/kg every 2 weeks in combination with interferon alfa.

Cervical Cancer: The recommended dose of Bevacizumab is 15 mg/kg every 3 weeks as an intravenous infusion administered in combination with one of the following chemotherapy regimens: paclitaxel and cisplatin, or paclitaxel and topotecan.

Platinum-Resistant Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer: The recommended dose is 10mg/kg every 2 weeks in combination with one of the following intravenous chemotherapy regimens: paclitaxel, pegylated liposomal doxorubicin, or topotecan (weekly); or 15 mg/kg every 3 weeks in combination with topotecan (every 3 weeks).

Platinum-Sensitive Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: The recommended dose is 15 mg/kg every 3 weeks when administered in combination with carboplatin and paclitaxel for 6 cycles and up to 8 cycles, followed by continued use of Bevacizumab 15 mg/kg every 3 weeks as a single agent until disease progression. Alternatively, 15 mg/kg every 3 weeks when administered in combination with carboplatin and gemcitabine for 6 cycles and up to 10 cycles, followed by continued use of Bevacizumab 15 mg/kg every 3 weeks as a single agent until disease progression.

Administration

Do not administer as an IV push or bolus. Do not initiate Bevacizumab for 28 days following major surgery (until surgical wound is fully healed).

First infusion: Administer infusion over 90 minutes.

Subsequent infusions: Administer second infusion over 60 minutes if first infusion is tolerated; administer all subsequent infusions over 30 minutes if infusion over 60 minutes is tolerated.

Preparation for Administration: Use appropriate aseptic technique. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Withdraw the necessary amount of Bevacizumab and dilute in a total volume of 100 ml of 0.9% Sodium Chloride injection, USP. Discard any unused portion left in a vial, as the product contains no preservatives.

A clinical interaction study evaluated irinotecan administered as part of the FOLFIRI regimen with or without Bevacizumab. The findings showed that Bevacizumab did not significantly alter the pharmacokinetics of irinotecan or its active metabolite SN-38.

No specific contraindications have been listed in the manufacturer’s prescribing information.

The most frequently reported adverse effects (occurring in more than 10% of patients and at least twice as often as in control groups) include nosebleeds, headache, high blood pressure, rhinitis, proteinuria, altered taste, dry skin, rectal bleeding, tear-related disorders, back pain, and exfoliative dermatitis.

Pregnancy: Based on findings from animal studies and its mechanism of action, Bevacizumab may cause harm to the fetus when administered during pregnancy. Therefore, it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: There is no available information regarding the presence of Bevacizumab in human milk, its effects on the breastfed infant, or its impact on milk production. Although human IgG is present in breast milk, it is unlikely to be absorbed in significant amounts by the infant. However, due to the possibility of serious adverse reactions, breastfeeding is not recommended during treatment with Bevacizumab.

Perforation or Fistula: Discontinue Bevacizumab if gastrointestinal perforation or fistula develops.

Arterial Thromboembolic Events (ATE): (e.g., myocardial infarction, stroke): Stop Bevacizumab in cases of severe ATE.

Venous Thromboembolic Events (VTE): Discontinue Bevacizumab in life-threatening VTE.

Hypertension: Regularly monitor blood pressure and manage hypertension. Temporarily withhold Bevacizumab if blood pressure is not controlled. Permanently discontinue in cases of hypertensive crisis or encephalopathy.

Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue Bevacizumab if PRES occurs.

Proteinuria: Monitor urinary protein levels. Discontinue Bevacizumab in nephrotic syndrome and temporarily interrupt therapy in moderate proteinuria.

Infusion Reactions: Stop treatment in case of severe infusion-related reactions.

Embryo-fetal Toxicity: Inform women of reproductive potential about the risk to the fetus and the importance of effective contraception.

Ovarian Failure: Inform female patients about the potential risk of ovarian dysfunction.

Pediatric Use: The safety, effectiveness, and pharmacokinetics of Bevacizumab in pediatric patients have not been established. Reports indicate cases of osteonecrosis in patients under 18 years treated with Bevacizumab. It is not approved for use in individuals below 18 years of age. Limited data are available regarding its safety and efficacy in children with glioblastoma. Animal studies have shown abnormalities in growth plates in juvenile subjects exposed to the drug, which were dose-related and partially reversible after discontinuation.

Geriatric Use in Study: In elderly patients (≥65 years), certain adverse events occurred more frequently compared to younger patients. These included asthenia, sepsis, deep vein thrombosis, hypertension, hypotension, myocardial infarction, congestive heart failure, diarrhea, constipation, anorexia, leukopenia, anemia, dehydration, hypokalemia, and hyponatremia. However, overall survival outcomes were similar between elderly and younger patients.

The highest tested dose in humans (20 mg/kg IV) was associated with headache in the majority of patients, with some experiencing severe headache.

Targeted Cancer Therapy

Store Bevacizumab vials in a refrigerator at 2°C to 8°C. Keep the vial in its original carton to protect from light. Do not freeze. Keep out of reach of children.