The FDA approved bevacizumab-bvzr (Zirabev, Pfizer), a biosimilar to bevacizumab (Avastin, Genentech), for the treatment of five types of cancer: metastatic colorectal cancer; unresectable, locally advanced, recurrent or metastatic nonsquamous non-small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma; and persistent, recurrent or metastatic cervical cancer.

The FDA approval was based on review of a comprehensive data package that demonstrated biosimilarity of bevacizumab-bvzr to the reference product. This includes results from the REFLECTIONS B7391003 clinical comparative study, which showed clinical equivalence and found no clinically meaningful differences between bevacizumab-bvzr and the reference product in patients with advanced nonsquamous NSCLC (Presented at: 2018 American Society of Clinical Oncology annual meeting; abstract 109).

“Zirabev represents a welcome addition to the treatment armamentarium in its approved indications, potentially providing physicians with a medicine that has a similar safety profile and efficacy as the reference product,” said Niels Reinmuth, MD, of the Department of Thoracic Oncology, Asklepios Lung Clinic, Munich-Gauting, Germany, and a lead author of the REFLECTIONS B7391003 study. “The FDA’s approval of Zirabev may provide an important new option for the treatment of multiple forms of cancer.”

This is the sixth biosimilar approval for Pfizer. Bevacizumab-bvzr is a monoclonal antibody biosimilar of the reference product, bevacizumab, which works by inhibiting angiogenesis by specifically recognizing and binding to vascular endothelial growth factor protein. As part of the REFLECTIONS clinical trial program, bevacizumab-bvzr has been studied in nearly 400 patients to date.

Across studies, the most common adverse reactions observed in bevacizumab patients at a rate greater than 10% were epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain and exfoliative dermatitis.

Across all studies, bevacizumab was discontinued in 8% to 22% of patients because of adverse reactions.

Serious and sometimes fatal gastrointestinal perforation occurred at a higher incidence in patients receiving bevacizumab products compared with those receiving chemotherapy.

The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in bevacizumab-treated patients. Thus, it should be withheld for at least 28 days before elective surgery and for at least 28 days after surgery until the wound is fully healed. It should be discontinued in patients who develop wound healing complications that require medical intervention or necrotizing fasciitis.

Severe or fatal hemorrhage, including hemoptysis, gastrointestinal bleeding, hematemesis, central nervous system hemorrhage, epistaxis and vaginal bleeding occurred up to fivefold more frequently in patients receiving bevacizumab.

In clinical studies, the incidence of grade 3 or higher hemorrhagic events among patients receiving bevacizumab ranged from 0.4% to 7%. Do not administer bevacizumab-bvzr to patients with serious hemorrhage or a recent history of hemoptysis (≥1/2 teaspoon of red blood). Discontinue bevacizumab-bvzr in patients who develop grade 3 to 4 hemorrhage.

Additional serious and sometimes fatal adverse events with increased incidence in the bevacizumab-treated arm versus chemotherapy arm included:

• arterial thromboembolic events;

• renal injury and proteinuria;

• nephrotic syndrome;

• venous thromboembolism;

• hypertension;

• posterior reversible encephalopathy syndrome;

• congestive heart failure; and

• infusion-related reactions with the first dose of bevacizumab.

Inform women of reproductive potential of the risk for ovarian failure before initiating treatment. On the basis of the mechanism of action and animal studies, bevacizumab products may cause fetal harm.

Advise women of reproductive potential to use effective contraception during treatment with bevacizumab-bvzr and for six months after the last dose of bevacizumab-bvzr. Advise nursing women that breastfeeding is not recommended during treatment with bevacizumab-bvzr and for six months after their last dose of treatment. For the full prescribing information, click here.

—Clinical Oncology News Staff