ZIRABEV

What it is

ZIRABEV is bevacizumab 100 mg/4 mL and 400 mg/16 mL concentrated solution for injection vials . ZIRABEV is a biosimilar medicine to Avastin . Bevacizumab is the active ingredient . Bevacizumab is an antineoplastic agent and a recombinant humanised monoclonal antibody that selectively binds to and neutralises the biologic activity of human vascular endothelial growth factor (VEGF) .

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 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 of unresectable disease . — 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 including chemotherapy . — Advanced epithelial ovarian, fallopian tube or primary peritoneal cancer (FIGO stages IIIB, IIIC and IV), in combination with carboplatin and paclitaxel, for first-line treatment . — First recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, in patients who have not received prior bevacizumab or other VEGF-targeted angiogenesis inhibitors . — Recurrent platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with paclitaxel, topotecan or pegylated liposomal doxorubicin, in patients who have received no more than two prior chemotherapy regimens and no prior anti-angiogenic therapy . — Persistent, recurrent or metastatic cervical carcinoma, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan as an alternative where cisplatin is not tolerated or not indicated .

Dosing overview

Dosing varies by indication and chemotherapy regimen used. For metastatic colorectal cancer, the recommended dose ranges from 5 mg/kg every 2 weeks (first-line) to 15 mg/kg every 3 weeks (second-line). For breast cancer and glioma, 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks is recommended. For non-small cell lung cancer, 15 mg/kg every 3 weeks is used. For renal cell cancer, 10 mg/kg every 2 weeks is given. For ovarian cancer and cervical cancer, 15 mg/kg every 3 weeks is standard . ZIRABEV should be administered under the supervision of a physician experienced in the use of antineoplastic medicines .

Key safety warnings

Patients may be at increased risk for gastrointestinal perforation and gallbladder perforation. ZIRABEV should be permanently discontinued in patients who develop gastrointestinal perforation . Patients treated for persistent, recurrent or metastatic cervical cancer may be at increased risk of fistulae between the vagina and the gastrointestinal tract, particularly those with prior pelvic radiation. Gastrointestinal perforations were reported in 3.2% and gastrointestinal-vaginal fistulae in 8.3% of bevacizumab-treated patients in one trial . An increased incidence of hypertension was observed in patients treated with bevacizumab. Pre-existing hypertension should be adequately controlled before starting treatment, and blood pressure monitoring is recommended during therapy . ZIRABEV 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 . ZIRABEV may adversely affect wound healing. 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 during elective surgery . An increased incidence of arterial thromboembolic events including cerebrovascular accidents, myocardial infarction and transient ischaemic attacks has been observed. ZIRABEV should be permanently discontinued in patients who develop arterial thromboembolic events . Patients with a history of arterial thromboembolism, diabetes or age greater than 65 years have an increased risk and caution should be exercised when treating such patients . Patients treated with bevacizumab have an increased risk of haemorrhage, especially tumour-associated haemorrhage. ZIRABEV should be permanently discontinued in patients who experience Grade 3 or 4 bleeding . Patients with non-small cell lung cancer treated with ZIRABEV may be at risk for serious, and in some cases fatal, pulmonary haemorrhage. Patients with recent pulmonary haemorrhage should not be treated . Patients with a history of hypertension may be at increased risk for proteinuria when treated with bevacizumab, and the incidence may be dose-dependent. Testing for proteinuria is recommended prior to starting therapy .

Contraindications

ZIRABEV 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 .

PBS listing

No PBS listing information has been provided in the available sources.

Regulatory history

The TGA approved ZIRABEV on 28 October 2019 . ZIRABEV was evaluated as a biosimilar medicine to the reference product Avastin, with the TGA finding the application acceptable for registration and supporting extrapolation to all currently approved indications of Avastin in Australia . In July 2022, the PBAC recommended ZIRABEV for metastatic colorectal cancer, advanced metastatic or recurrent non-squamous non-small cell lung cancer, relapsed or recurrent glioblastoma, epithelial ovarian fallopian tube or primary peritoneal cancer, and cervical cancer, with recommendation extended 12 months .