Bevacizumab (Avastin)

Last updated 4/26/25

What It Is

Bevacizumab is a humanized monoclonal antibody that binds vascular endothelial growth factor A (VEGF-A), preventing it from activating VEGF receptors on endothelial cells. The result is pruning of tumor vasculature, reduced edema, and transient normalization of blood–brain barrier permeability.

Names & Formulations (USA)

• Brand: Avastin® (Genentech/Roche) — supplied as 100 mg/4 mL and 400 mg/16 mL single-use vials.
• Biosimilars: Mvasi, Zirabev, Alymsys, Vegzelma, Avzivi, and others (all FDA‑licensed as interchangeable).

How It Is Used

Dosing is weight-based. FDA approved schedules are 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks in solid tumors. For brain tumors, the following empiric regimens are common:

Setting	Typical Schedule	Key Points
Recurrent high-grade glioma	10 mg/kg q2w or 15 mg/kg q3w	Steroid-sparing; monitor blood pressure, proteinuria, and risk of thrombosis.
Newly diagnosed GBM (off-label)	10 mg/kg q2w starting week 4 of chemoradiation	PFS benefit without OS gain in phase III trials.
Radiation necrosis / pseudoprogression	7.5 mg/kg q2w for 2-4 doses	Rapid reduction of edema; course can be stopped once symptoms resolve.

Controversy over dose: Several retrospective and prospective studies suggest that a lower dose of 5 mg/kg q2w or q3w may achieve similar progression-free and overall survival with fewer grade 3/4 adverse events and lower cost. Key low-dose studies include: Kaloshi 2013, Melhem 2023, and Blumenthal 2025.

Regulatory Status (U.S.)

• FDA-approved for multiple non-CNS cancers; granted accelerated approval for recurrent glioblastoma in 2009.
• NCCN Guidelines list bevacizumab as Category 2A for recurrent GBM and radiation necrosis.
• More than half a dozen biosimilars received approval 2017-2024.

Key Research Highlights

• BRAIN 2009 - Phase II in recurrent GBM: PFS6 42%, median OS 9.3 months.
• AVAglio 2014 - Newly diagnosed GBM: improved PFS but no OS benefit.
• RTOG 0825 2014 - Similar PFS benefit, neurocognitive decline noted, no OS gain.
• EORTC 26101 2017 - Lomustine + bevacizumab prolonged PFS, no OS advantage.
• Melhem 2023 - Dose‑dependent efficacy: 5 mg/kg as effective as 10 mg/kg with fewer toxicities.

Biomarkers & Response Prediction

No validated predictive biomarker exists. Elevated circulating VEGF, perfusion MRI metrics, and early steroid‑sparing response are under investigation but are not yet ready for clinical decision-making.

Further Reading

• Musella A. Brain Tumor Guide for the Newly Diagnosed, v12 - pp 190-195.
• Narita Y. Drug review: safety and efficacy of bevacizumab for glioblastoma. Jpn J Clin Oncol 2013.