Bevacizumab (Avastin)

General information

Class/mechanism: Monoclonal antibody that inhibits angiogenesis by binding VEGF and preventing the interaction of VEGF with its receptors (Flt-1 and KDR) on the surface of endothelial cells.
Route: IV
Extravasation: neutral

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, Medscape,UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

• Carcinoma of unknown primary
• Anaplastic glioma
• Breast cancer
• Cervical cancer
• Cholangiocarcinoma
• Colorectal cancer
• Esophageal cancer
• Follicular lymphoma
• Glioblastoma
• Hepatocellular carcinoma
• Kaposi sarcoma
• Melanoma
• Mesothelioma
• Neuroendocrine tumor
• Non-small cell lung cancer
• Ovarian cancer
• Pancreatic NET
• Renal cell carcinoma
• Small cell lung cancer
• Testicular cancer
• Endometrial cancer
• Vascular sarcoma

Information about counterfeit bevacizumab

• FDA's 2/14/2012 statement about counterfeit Avastin in U.S.
• Genentech's 2/14/2012 statement on counterfeit drug labeled as Avastin (Bevacizumab) in the United States - contains pictures of authentic and counterfeit product
• Authorized specialty distributors, wholesalers and specialty pharmacies for Bevacizumab (Avastin)

Patient drug information

• Bevacizumab (Avastin) patient drug information (Chemocare)
• Brief patient counseling information can be found in the package insert
• Bevacizumab (Avastin) patient drug information (UpToDate)

History of changes in FDA indication

Breast cancer - WITHDRAWN

• 2/22/2008: Granted accelerated approval for use in combination with paclitaxel for the treatment of patients who have not received chemotherapy for metastatic HER2 negative breast cancer. (New disease entity; based on ECOG E2100)
  • 11/18/2011: Approval withdrawn. (Based on AVADO & RIBBON-1)
    • Note: this withdrawal is considered to be controversial, and the breast cancer indication remains in the EMA approval. This article provides a good overview.

Cervical cancer

• 8/14/2014: Approved for treatment of cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease. (Based on GOG 240)

Colorectal cancer

• 2/26/2004: Initial FDA approval, in combination with intravenous 5-fluorouracil–based chemotherapy...for first- line treatment of patients with metastatic carcinoma of the colon or rectum. (Based on AVF2107g)
• 6/20/2006: Approved for second-line treatment of metastatic carcinoma of the colon or rectum. (New treatment setting without explicit requirement for combination therapy; based on ECOG E3200 & TRC-301)
• 1/23/2013: Approved for use in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed on a first-line bevacizumab-containing regimen. (Based on ML18147)
• Metastatic colorectal cancer, with intravenous 5-fluorouracil–based chemotherapy for first- or second-line treatment.
• Limitation: Lack of efficacy in adjuvant treatment of colon cancer. (Based on AVANT & NSABP C-08)

Glioblastoma

• 5/5/2009: Granted accelerated approval as a single agent for patients with glioblastoma, with progressive disease following prior therapy. (Based on NCI 06-C-0064E & AVF3708g)
• 12/5/2017: Converted to regular approval for patients with glioblastoma with progressive disease following prior therapy. (Based on EORTC 26101)

Hepatocellular carcinoma

• 5/29/2020: Approved in combination with atezolizumab for patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy. (Based on IMbrave150)

Non-small cell lung cancer

• 10/11/2006: Approved as a first-line treatment of patients with locally advanced, metastatic or recurrent non-small cell lung cancer in combination with platinum-based chemotherapy.
  • Non-squamous non-small cell lung cancer, with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease. (Label restricted to non-squamous histology only; based on ECOG E4599 & AVAil)

Ovarian cancer

• 11/14/2014: Approved for treatment of platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan. (Based on AURELIA)
• 12/6/2016: Approved for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer that is platinum-sensitive in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine, followed by Avastin as a single agent. (Based on NRG/GOG-0213 and OCEANS)
• 6/13/2018: FDA approved for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab, for stage III or IV disease after initial surgical resection. (Indication expanded to first-line setting; based on GOG-0218)

Renal cell carcinoma

• 7/31/2009: Approved in combination with interferon alfa for the treatment of patients with metastatic renal cell carcinoma. (Based on AVOREN)

History of changes in EMA indication

• 1/12/2005: Initial market authorization as Avastin.

Also known as

• Generic name: rhuMab-VEGF
• Brand names: Altuzan, Avastin, BevaciRel, Bevarest