Bevacizumab

Bevacizumab is a recombinant humanised monoclonal antibody belonging to the vascular endothelial growth factor, or VEGF, inhibitor class of targeted anticancer medicines. It binds to VEGF and prevents VEGF from activating its receptors on vascular endothelial cells, thereby reducing the formation and maintenance of new blood vessels that tumors can use for growth and survival. Bevacizumab is administered intravenously and is generally used in combination with chemotherapy, immunotherapy or other anticancer treatment rather than as conventional cytotoxic monotherapy. Depending on the regulatory jurisdiction and cancer type, it is used for metastatic colorectal cancer, non-squamous non-small cell lung cancer, recurrent or advanced ovarian and related gynecologic cancers, cervical cancer, renal cell carcinoma, recurrent glioblastoma and selected hepatocellular carcinoma settings. Treatment schedules vary by indication and commonly range from every two weeks to every three weeks. Because VEGF inhibition can affect blood vessels and normal tissue repair, clinically important monitoring is required for blood pressure, proteinuria, bleeding, thrombosis, wound healing, gastrointestinal complications and infusion-related reactions. Bevacizumab should be administered under the supervision of healthcare professionals experienced in anticancer therapy.

Bevacizumab was developed as a humanised monoclonal antibody designed to neutralize VEGF and inhibit tumor-associated angiogenesis. The U.S. Food and Drug Administration granted its initial approval in February 2004 for metastatic colorectal cancer in combination with fluorouracil-based chemotherapy. Subsequent U.S. approvals expanded its use to selected non-squamous non-small cell lung cancer, recurrent glioblastoma, metastatic renal cell carcinoma, cervical cancer, ovarian and related gynecologic cancers, and unresectable or metastatic hepatocellular carcinoma in combination with atezolizumab. The European Commission granted marketing authorisation for Avastin on 12 January 2005, with the European indication subsequently covering metastatic colorectal cancer, selected breast cancer settings, non-squamous non-small cell lung cancer, renal cell carcinoma, ovarian, fallopian tube and primary peritoneal cancers, and cervical cancer. Indian regulatory records document bevacizumab products and subsequent approvals of additional indications, including recurrent ovarian cancer and the combination of bevacizumab with atezolizumab for unresectable or metastatic hepatocellular carcinoma in patients without prior systemic therapy. Major clinical development programmes include AVF2107g, E2100, AVAiL, RIBBON, GOG-0218, ICON7, AVAglio and IMbrave150.

Bevacizumab is used in combination with other anticancer medicines for selected advanced or metastatic cancers. In metastatic colorectal cancer, it is combined with fluoropyrimidine-based chemotherapy and may be used with irinotecan- or oxaliplatin-based regimens depending on the treatment line. In non-squamous non-small cell lung cancer, it is used with platinum-based chemotherapy in appropriate patients, while selected EGFR-mutated non-squamous disease may be treated with bevacizumab plus erlotinib in applicable regulatory settings. It is also used for recurrent glioblastoma, metastatic renal cell carcinoma, persistent, recurrent or metastatic cervical cancer, and advanced epithelial ovarian, fallopian tube or primary peritoneal cancer in specified treatment settings. In hepatocellular carcinoma, bevacizumab is used with atezolizumab for unresectable or metastatic disease in patients who have not received prior systemic therapy where this combination is approved. Treatment selection depends on cancer type, disease stage, previous therapy, tumor characteristics, overall clinical condition and the approved indication applicable to the specific jurisdiction.

Bevacizumab is administered by intravenous infusion, with dosing determined by the cancer type and treatment regimen. Common adult regimens include 5 or 10 mg per kg every two weeks for selected colorectal cancer settings, 15 mg per kg every three weeks with chemotherapy for first-line non-squamous non-small cell lung cancer, 10 mg per kg every two weeks for recurrent glioblastoma and metastatic renal cell carcinoma, and 15 mg per kg every three weeks for selected cervical and ovarian cancer regimens. When used with atezolizumab for hepatocellular carcinoma, the commonly approved regimen is 15 mg per kg every three weeks. The first infusion is generally administered slowly, with subsequent infusions given more rapidly if the initial dose is well tolerated. Treatment is usually continued until disease progression or unacceptable toxicity, although some indications specify a defined duration or continuation as maintenance after chemotherapy. Bevacizumab should be withheld around major surgery and should not be restarted until adequate wound healing has occurred.

Common side effects of bevacizumab include high blood pressure, fatigue, weakness, diarrhea, abdominal discomfort, headache, nausea, decreased appetite and protein in the urine. Patients receiving bevacizumab with chemotherapy may also experience adverse effects associated with the accompanying anticancer medicines, including reduced blood counts, infection, nausea, vomiting and neuropathy. Infusion-related reactions can include fever, chills, flushing, changes in blood pressure or other symptoms occurring during or shortly after administration. The frequency and severity of adverse effects vary according to the cancer type, treatment combination, dose and individual patient characteristics. Blood pressure and urine protein should be monitored regularly, and supportive treatment or treatment modification may be required when clinically significant adverse effects develop.

Important serious risks associated with bevacizumab include gastrointestinal perforation, fistula formation, serious bleeding, arterial or venous thromboembolic events, severe hypertension, proteinuria, kidney-related complications, impaired wound healing and infusion-related reactions. Rare but serious neurologic complications such as posterior reversible encephalopathy syndrome can occur. Bevacizumab may also cause ovarian failure in premenopausal women and can affect fertility. Because VEGF inhibition interferes with normal blood-vessel repair, treatment can increase the risk of surgical and wound-healing complications and should be appropriately withheld around major surgery. Gastrointestinal perforation can occur and may require permanent discontinuation. Severe hypertension should be controlled before and during treatment, while significant proteinuria may require interruption or discontinuation. Bevacizumab can cause fetal harm, and pregnancy should be avoided during treatment and for the required period after the final dose according to the applicable prescribing information.

Before starting bevacizumab, healthcare professionals should assess blood pressure, urine protein, renal function, bleeding and thrombotic history, gastrointestinal risk, wound-healing status and recent or planned surgical procedures. Patients with uncontrolled hypertension, significant bleeding risk, active gastrointestinal complications or recent major surgery require careful clinical assessment. Bevacizumab is not primarily metabolized through conventional CYP enzyme pathways, so classic CYP-mediated drug interactions are not a major concern. However, additive toxicity can occur when bevacizumab is combined with chemotherapy, immunotherapy, anticoagulants or antiplatelet medicines, particularly with respect to bleeding, thrombosis, hypertension or impaired wound healing. Live vaccines and other concomitant medicines should be reviewed according to the complete treatment regimen. Patients should inform their healthcare team about planned surgery, dental procedures, anticoagulant use and any new bleeding, abdominal pain, severe headache, vision changes or other significant symptoms during treatment.

Prescribers should confirm the cancer diagnosis, disease stage, previous treatment and precise regulatory indication before initiating bevacizumab. Baseline assessment should include blood pressure, urine protein, renal function, bleeding and thrombotic risk, recent surgery and gastrointestinal history. Pharmacists should verify the weight-based dose, treatment interval, combination chemotherapy or immunotherapy and infusion requirements before dispensing. Particular attention should be given to surgical timing because bevacizumab can impair wound healing and generally requires a treatment interruption around major surgery. Patients should be counselled to report severe abdominal pain, unusual bleeding, severe headache, chest pain, shortness of breath, sudden weakness, visual changes, reduced urine output or poorly controlled blood pressure promptly. When bevacizumab is combined with atezolizumab or chemotherapy, monitoring should account for the adverse-effect profile of the entire regimen. Coordination between oncology, pharmacy, nursing, laboratory and surgical teams helps ensure appropriate administration and timely management of toxicity.