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.Bevacizumab (Avastin) package insert Bevacizumab (Avastin) package insert (locally hosted backup)Avastin manufacturer's website
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, UpToDate Lexidrug, Medscape,or the prescribing information.
==Diseases for which it is established (work in progress)==
*Cervical cancer
*Colorectal cancer
*Glioblastoma
*Hepatocellular carcinoma
*Malignant pleural mesothelioma
*Non-small cell lung cancer, nonsquamous
*Ovarian cancer
*Renal cell carcinoma
==Diseases for which it is used==
*Carcinoma of unknown primary
*Anaplastic glioma
*Angiosarcoma
*Breast cancer
*Cholangiocarcinoma
*Endometrial cancer
*Esophageal cancer
*Follicular lymphoma
*Gallbladder cancer
*Gastric cancer
*Kaposi sarcoma
*Malignant peritoneal mesothelioma
*Melanoma 
*Neuroendocrine tumor
*Non-small cell lung cancer
*Pancreatic NET
*Small cell lung cancer
*Testicular cancer
*Urothelial carcinoma
==Information about counterfeit bevacizumab==
*FDA's 2012-02-14 statement about counterfeit Avastin in U.S.
*Genentech's 2012-02-14 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)Bevacizumab (Avastin) patient drug information (Chemocare)
*Brief patient counseling information can be found in the package insert
*Bevacizumab (Avastin) patient drug information (UpToDate)Bevacizumab (Avastin) patient drug information (UpToDate)
==History of changes in FDA indication==
===Breast cancer - WITHDRAWN===
*2008-02-22: 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)
**2011-11-18: Accelerated approval for metastatic HER2 negative breast cancer 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===
*2014-08-14: 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===
*2004-02-26: 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)
*2006-06-20: 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)
*2013-01-23: 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===
*2009-05-05: Granted accelerated approval as a single agent for patients with glioblastoma, with progressive disease following prior therapy. (Based on NCI 06-C-0064E & AVF3708g)
**2017-12-05: Converted to regular approval for patients with glioblastoma with progressive disease following prior therapy. (Based on EORTC 26101)
===Hepatocellular carcinoma===
*2020-05-29: 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, nonsquamous===
*2006-10-11: Approved for non-squamous, non-small cell lung cancer, with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease. (New disease entity; based on ECOG E4599 & AVAil)
===Ovarian cancer===
*2014-11-14: 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)
*2016-12-06: 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)
*2018-06-13: 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===
*2009-07-31: 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==
*2005-01-12: Initial market authorization as Avastin in combination with intravenous 5-fluorouracil/folinic acid or intravenous 5-fluorouracil/folinic acid/irinotecan for first-line treatment of patients with metastatic carcinoma of the colon or rectum. (Based on AVF2107g & AVF0780g)
*2011-12-19: Extension of indication to include the use of Avastin, in combination with carboplatin and paclitaxel for the front-line treatment of advanced (FIGO stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.
*2014-07-31: Extension of indication to include Avastin in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin for the treatment of adult patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents.
*2015-03-30: Extension of Indication to include treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix for Bevacizumab in combination with paclitaxel and cisplatin or paclitaxel and topotecan.
*2016-06-02: Extension of indication to include the combination of bevacizumab with erlotinib for the first line treatment of patients with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) activating mutations.
*2017-06-02: Extension of indication to include the use of Avastin in combination with paclitaxel and carboplatin for the for treatment of adult patients with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents.
==History of changes in Health Canada indication==
*2005-09-09: Initial notice of compliance.
*2011-11-25: Avastin used in combination with paclitaxel is indicated for the treatment of patients with metastatic HER2-negative breast cancer and who are ECOG Class 0-1, has been suspended.
*2018-05-23: Avastin, as a single agent, for the treatment of patients with glioblastoma (GBM) after relapse or disease progression, following prior therapy, has been withdrawn.
==History of changes in PMDA indication==
*2007-04-18: Initial approval for the treatment of unresectable advanced/relapsed colorectal cancer.
*2009-09-18: New additional indication for combination therapy with other anticancer drugs (XELOX + BV regimen) for advanced or recurrent colorectal cancer not suited for curative resection.
*2009-11-06: New additional indication and a new dosage for the treatment of unresectable advanced or recurrent non-squamous non-small cell lung cancer.
*2011-09-26: New additional indication and a new dosage for the treatment of unresectable or recurrent breast cancer.
*2013-06-14: New additional indication and a new dosage for the treatment of malignant glioma.
*2013-11-22: New additional indication for the treatment of ovarian cancer.
*2016-05-23: New additional indication for the treatment of advanced or recurrent cervical cancer.
*2020-09-25: New indication and a new dosage for the treatment of unresectable hepatocellular carcinoma.
==Also known as==
*Generic name: rhuMab-VEGF
*Brand names: Abevmy, Advamab, Altuzan, Avastin, Bevacizab, Bevaro, Bevarest, Bevatas, Bevazza, BevaciRel, Bryxta, Cizumab, Krabeva
==References==
Category:Drugs
Category:Intravenous medications
Category:Neutral
Category:Anti-VEGF antibodies
Category:Carcinoma of unknown primary medications
Category:Anaplastic glioma medications
Category:Angiosarcoma medications
Category:Breast cancer medications
Category:Cervical cancer medications
Category:Cholangiocarcinoma medications
Category:Colorectal cancer medications
Category:Endometrial cancer medications
Category:Esophageal cancer medications
Category:Follicular lymphoma medications
Category:Gallbladder cancer medications
Category:Gastric cancer medications
Category:Glioblastoma medications
Category:Hepatocellular carcinoma medications
Category:Kaposi sarcoma medications
Category:Malignant peritoneal mesothelioma medications
Category:Malignant pleural mesothelioma medications
Category:Melanoma medications 
Category:Neuroendocrine tumor medications
Category:Non-small cell lung cancer medications
Category:Non-small cell lung cancer, nonsquamous medications
Category:Ovarian cancer medications
Category:Pancreatic NET medications
Category:Renal_cell_carcinoma medications
Category:Small cell lung cancer medications
Category:Testicular cancer medications
Category:Urothelial carcinoma medications
Category:EMA approved in 2005
Category:FDA approved in 2004
Category:Health Canada approved in 2005
Category:PMDA approved in 2007