BEVACIP

What it is

BEVACIP is bevacizumab 100 mg/4 mL and 400 mg/16 mL concentrated solution for infusion in vials. BEVACIP is a biosimilar medicine to Avastin. The evidence for comparability supports the use of BEVACIP for the listed indications. Bevacizumab is a recombinant humanised monoclonal antibody that selectively binds to and neutralises the biologic activity of human vascular endothelial growth factor (VEGF). Bevacizumab inhibits the binding of VEGF to its receptors on the surface of endothelial cells, and neutralising the biologic activity of VEGF reduces the vascularisation of tumours, thereby inhibiting tumour growth.

Approved indications

— Metastatic colorectal cancer, in combination with fluoropyrimidine-based chemotherapy. — Locally recurrent or metastatic breast cancer, in combination with paclitaxel for first-line treatment in patients in whom an anthracycline-based therapy is contraindicated. — Advanced, metastatic or recurrent non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment. — Advanced and/or metastatic renal cell cancer, in combination with interferon alfa-2a. — Grade IV glioma as a single agent for treatment after relapse or disease progression after standard therapy. — Advanced epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with carboplatin and paclitaxel for first-line treatment. — Recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with carboplatin and paclitaxel or carboplatin and gemcitabine for first recurrence of platinum-sensitive disease, or in combination with paclitaxel, topotecan or pegylated liposomal doxorubicin for recurrent platinum-resistant disease. — Persistent, recurrent or metastatic cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.

Dosing overview

For metastatic colorectal cancer, first-line treatment requires 5 mg/kg intravenously every 2 weeks or 7.5 mg/kg every 3 weeks; second-line treatment requires 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks. For locally recurrent or metastatic breast cancer, the recommended dose is 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks. For advanced, metastatic or recurrent non-squamous non-small cell lung cancer, the recommended dose is 15 mg/kg every 3 weeks. For advanced and/or metastatic renal cell cancer, the recommended dose is 10 mg/kg every 2 weeks. For Grade IV glioma, the recommended dose is 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks. For epithelial ovarian, fallopian tube or primary peritoneal cancer first-line treatment, the recommended dose is 15 mg/kg every 3 weeks for up to 6 cycles with chemotherapy followed by continued BEVACIP monotherapy for a total of 15 months or until disease progression. For cervical cancer, the recommended dose is 15 mg/kg every 3 weeks until progression of the underlying disease. The initial infusion should be delivered over 90 minutes; if well tolerated, the second infusion may be given over 60 minutes, and if that is well tolerated, subsequent infusions may be given over 30 minutes.

Key safety warnings

Patients may be at increased risk for gastrointestinal perforation and gallbladder perforation when treated with BEVACIP, and bevacizumab should be permanently discontinued in patients who develop gastrointestinal perforation. Fatal outcome was reported in approximately a third of serious cases of gastrointestinal perforations, representing between 0.2% and 1% of all bevacizumab-treated patients. An increased incidence of hypertension was observed in patients treated with bevacizumab, and clinical safety data suggest that the incidence is likely to be dose-dependent. Pre-existing hypertension should be adequately controlled before starting bevacizumab treatment. Bevacizumab should be permanently discontinued if medically significant hypertension cannot be adequately controlled with antihypertensive therapy, or if the patient develops hypertensive crisis or hypertensive encephalopathy. Bevacizumab may adversely affect the wound healing process; therapy should not be initiated for at least 28 days following major surgery or until the surgical wound is fully healed, and should be withheld in patients who experience wound healing complications during therapy. Serious wound healing complications, including anastomotic complications, have been reported, some of which had a fatal outcome. An increased incidence of arterial thromboembolic events including cerebrovascular accidents, myocardial infarction and transient ischaemic attacks has been observed, with an overall incidence ranging up to 5.9% in bevacizumab-containing arms compared with up to 1.7% in chemotherapy control arms. Bevacizumab should be permanently discontinued in patients who develop arterial thromboembolic events. Patients treated with bevacizumab have an increased risk of haemorrhage, especially tumour-associated haemorrhage, and bevacizumab should be permanently discontinued in patients who experience Grade 3 or 4 bleeding. Patients with non-small cell lung cancer treated with bevacizumab may be at risk for serious and in some cases fatal pulmonary haemorrhage or haemoptysis; patients with recent pulmonary haemorrhage or haemoptysis should not be treated with bevacizumab. Patients with a history of hypertension may be at increased risk for the development of proteinuria when treated with bevacizumab, and there is evidence suggesting that all grade proteinuria may be dose-dependent; testing for proteinuria is recommended prior to the start of bevacizumab therapy.

Contraindications

BEVACIP is contraindicated in patients with known hypersensitivity to any components of the product, Chinese hamster ovary cell products or other recombinant human or humanised antibodies.

Regulatory history

The TGA approved BEVACIP (bevacizumab) on 13 October 2021. The approval was based on the evaluation finding no objections on quality grounds and the sponsor demonstrating comparability to the reference product, Avastin. BEVACIP bevacizumab 100 mg/4 mL and 400 mg/16 mL concentrated solution for infusion vials were first listed on the ARTG on 2 November 2021.