Difference between revisions of "Bevacizumab (Avastin)"

Revision as of 11:18, 9 April 2024

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.^[1]^[2]^[3]
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.^[1]

Diseases for which it is established (work in progress)

Diseases for which it is used

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)^[4]
Brief patient counseling information can be found in the package insert^[1]
Bevacizumab (Avastin) patient drug information (UpToDate)^[5]

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Breast cancer - WITHDRAWN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- 2011-11-18: Accelerated approval for metastatic HER2 negative breast cancer withdrawn.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 staqes 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 peqylated 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-tarqeted aqents.
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) activatinq 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-tarqeted aqents.

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: Altuzan, Avastin, BevaciRel, Bevarest

References

[insert-1] 1.0 ^1.1 ^1.2 Bevacizumab (Avastin) package insert

[2] Bevacizumab (Avastin) package insert (locally hosted backup)

[3] Avastin manufacturer's website

[4] Bevacizumab (Avastin) patient drug information (Chemocare)

[5] Bevacizumab (Avastin) patient drug information (UpToDate)

[1]

[2]

[3]

[4]

[5]

@@ Line 5: / Line 5: @@
 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 [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://reference.medscape.com/drug/avastin-bevacizumab-342257 Medscape],[http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>
+==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==
@@ Line 10: / Line 20: @@
 *[[Carcinoma of unknown primary]]
 *[[Anaplastic glioma]]
+*[[Angiosarcoma]]
 *[[Breast cancer]]
-*[[Cervical cancer]]
 *[[Cholangiocarcinoma]]
-*[[Colon cancer]]
+*[[Endometrial cancer]]
 *[[Esophageal cancer]]
 *[[Follicular lymphoma]]
-*[[Glioblastoma]]
+*[[Gallbladder cancer]]
-*[[Hepatocellular carcinoma]]
+*[[Gastric cancer]]
 *[[Kaposi sarcoma]]
+*[[Malignant peritoneal mesothelioma]]
 *[[Melanoma]]
-*[[Mesothelioma]]
 *[[Neuroendocrine tumor]]
 *[[Non-small cell lung cancer]]
-*[[Ovarian cancer]]
 *[[Pancreatic NET]]
-*[[Renal cell carcinoma]]
 *[[Small cell lung cancer]]
 *[[Testicular cancer]]
-*[[Endometrial cancer]]
+*[[Urothelial carcinoma]]
-*[[Vascular sarcoma]]
 </div>
 ==Information about counterfeit bevacizumab==
-*[http://www.fda.gov/drugs/drugsafety/ucm291960.htm FDA's 2/14/2012 statement about counterfeit Avastin in U.S.]
+*[http://www.fda.gov/drugs/drugsafety/ucm291960.htm FDA's 2012-02-14 statement about counterfeit Avastin in U.S.]
-*[http://www.gene.com/gene/news/press-releases/press_statements/ps_021412.html Genentech's 2/14/2012 statement on counterfeit drug labeled as Avastin (Bevacizumab) in the United States] - contains pictures of authentic and counterfeit product
+*[http://www.gene.com/gene/news/press-releases/press_statements/ps_021412.html Genentech's 2012-02-14 statement on counterfeit drug labeled as Avastin (Bevacizumab) in the United States] - contains pictures of authentic and counterfeit product
 *[http://www.genentechaccesssolutions.com/portal/site/AS/menuitem.7ef3b8542d7c63460313edacd79c23a0/?vgnextoid=359169cc87727210VgnVCM1000007dc9320aRCRD&vgnextchannel=268c57e77eb07210VgnVCM1000007dc9320aRCRD Authorized specialty distributors, wholesalers and specialty pharmacies for Bevacizumab (Avastin)]
 ==Patient drug information==
-*[http://chemocare.com/chemotherapy/drug-info/bevacizumab.aspx Bevacizumab (Avastin) patient drug information (Chemocare)]<ref>[http://chemocare.com/chemotherapy/drug-info/bevacizumab.aspx Bevacizumab (Avastin) patient drug information (Chemocare)]</ref>
+*[https://chemocare.com/druginfo/bevacizumab.aspx Bevacizumab (Avastin) patient drug information (Chemocare)]<ref>[https://chemocare.com/druginfo/bevacizumab.aspx Bevacizumab (Avastin) patient drug information (Chemocare)]</ref>
 *Brief patient counseling information can be found in [http://www.gene.com/download/pdf/avastin_prescribing.pdf the package insert]<ref name="insert"></ref>
 *[http://www.uptodate.com/contents/bevacizumab-patient-drug-information Bevacizumab (Avastin) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/bevacizumab-patient-drug-information Bevacizumab (Avastin) patient drug information (UpToDate)]</ref>
@@ Line 44: / Line 51: @@
 ==History of changes in FDA indication==
 ===[[Breast cancer]] - '''WITHDRAWN'''===
-*2/22/2008: Granted accelerated approval for use in combination with [[Paclitaxel (Taxol)|paclitaxel]] for the treatment of patients who have not received chemotherapy for metastatic [[Breast_cancer|HER2 negative breast cancer]]. ''(New disease entity; based on ECOG E2100)''
+*2008-02-22: Granted accelerated approval for use in combination with [[Paclitaxel (Taxol)|paclitaxel]] for the treatment of patients who have not received chemotherapy for metastatic [[Breast_cancer|HER2 negative breast cancer]]. ''(New disease entity; based on ECOG E2100)''
-**11/18/2011: Approval withdrawn. ''(Based on AVADO & RIBBON-1)''
+**2011-11-18: Accelerated approval for metastatic [[Breast_cancer|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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744967/ This article] provides a good overview.
 ===[[Cervical cancer]]===
-*8/14/2014: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm410128.htm Approved] for treatment of [[Cervical_cancer|cervical cancer]], in combination with [[Paclitaxel (Taxol)|paclitaxel]] and [[Cisplatin (Platinol)|cisplatin]] or [[Paclitaxel (Taxol)|paclitaxel]] and [[Topotecan (Hycamtin)|topotecan]] in persistent, recurrent, or metastatic disease. ''(Based on GOG 240)''
+*2014-08-14: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm410128.htm Approved] for treatment of [[Cervical_cancer|cervical cancer]], in combination with [[Paclitaxel (Taxol)|paclitaxel]] and [[Cisplatin (Platinol)|cisplatin]] or [[Paclitaxel (Taxol)|paclitaxel]] and [[Topotecan (Hycamtin)|topotecan]] in persistent, recurrent, or metastatic disease. ''(Based on GOG 240)''
-===[[:Category:Colorectal_cancers|Colorectal cancer]]===
+===[[Colorectal cancer]]===
-*'''2/26/2004: [http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/125085ltr.pdf Initial FDA approval]''', in combination with intravenous [[Regimen_classes#5-FU-based_regimen|5-fluorouracil–based chemotherapy]]...for first- line treatment of patients with metastatic carcinoma of the [[Colon_cancer|colon]] or [[Rectal_cancer|rectum]]. ''(Based on AVF2107g)''
+*'''2004-02-26: [http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/125085ltr.pdf Initial FDA approval]''', in combination with intravenous [[Regimen_classes#5-FU-based_regimen|5-fluorouracil-based chemotherapy]]...for first- line treatment of patients with metastatic carcinoma of the [[Colon_cancer|colon]] or [[Rectal_cancer|rectum]]. ''(Based on AVF2107g)''
-*6/20/2006: Approved for second-line treatment of metastatic carcinoma of the [[Colon_cancer|colon]] or [[Rectal_cancer|rectum]]. ''(New treatment setting without explicit requirement for combination therapy; based on ECOG E3200 & TRC-301)''
+*2006-06-20: Approved for second-line treatment of metastatic carcinoma of the [[Colon_cancer|colon]] or [[Rectal_cancer|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 [[:Category:Colorectal_cancers|colorectal cancer]] (mCRC) whose disease has progressed on a first-line [[Regimen_classes#Bevacizumab-containing_regimen|bevacizumab-containing regimen]]. ''(Based on ML18147)''
+*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 [[Regimen_classes#Bevacizumab-containing_regimen|bevacizumab-containing regimen]]. ''(Based on ML18147)''
-*Metastatic [[:Category:Colorectal_cancers|colorectal cancer]], with intravenous [[Regimen_classes#5-FU-based_regimen|5-fluorouracil–based chemotherapy]] for first- or second-line treatment.
+*Metastatic [[colorectal cancer]], with intravenous [[Regimen_classes#5-FU-based_regimen|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)''
+*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)''
-*12/5/2017: Converted to regular approval for patients with [[glioblastoma]] with progressive disease following prior therapy. ''(Based on EORTC 26101)''
+**2017-12-05: 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 (Tecentriq)|atezolizumab]] for patients with unresectable or metastatic [[hepatocellular carcinoma]] who have not received prior systemic therapy. ''(New disease entity)''
+*2020-05-29: Approved in combination with [[Atezolizumab (Tecentriq)|atezolizumab]] for patients with unresectable or metastatic [[hepatocellular carcinoma]] who have not received prior systemic therapy. ''(Based on IMbrave150)''
-===[[Non-small cell lung cancer]]===
+===[[Non-small cell lung cancer, nonsquamous]]===
-*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 [[Regimen_classes#Platinum-based_regimen|platinum-based chemotherapy]].
+*2006-10-11: Approved for [[Non-small cell lung cancer, nonsquamous|'''non-squamous''', non-small cell lung cancer]], with [[Carboplatin (Paraplatin)|carboplatin]] and [[Paclitaxel (Taxol)|paclitaxel]] for first line treatment of unresectable, locally advanced, recurrent or metastatic disease. ''(New disease entity; based on ECOG E4599 & AVAil)''
-**[[Non-small_cell_lung_cancer|'''Non-squamous''' non-small cell lung cancer]], with [[Carboplatin (Paraplatin)|carboplatin]] and [[Paclitaxel (Taxol)|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: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm423159.htm Approved] for treatment of platinum-resistant recurrent [[Ovarian_cancer|epithelial ovarian, fallopian tube or primary peritoneal cancer]], in combination with [[Paclitaxel (Taxol)|paclitaxel]], [[Pegylated liposomal doxorubicin (Doxil)|pegylated liposomal doxorubicin]] or [[Topotecan (Hycamtin)|topotecan]]. ''(Based on AURELIA)''
+*2014-11-14: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm423159.htm Approved] for treatment of platinum-resistant recurrent [[Ovarian_cancer|epithelial ovarian, fallopian tube or primary peritoneal cancer]], in combination with [[Paclitaxel (Taxol)|paclitaxel]], [[Pegylated liposomal doxorubicin (Doxil)|pegylated liposomal doxorubicin]] or [[Topotecan (Hycamtin)|topotecan]]. ''(Based on AURELIA)''
-*12/6/2016: Approved for recurrent [[Ovarian_cancer|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)''
+*2016-12-06: Approved for recurrent [[Ovarian_cancer|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: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-bevacizumab-combination-chemotherapy-ovarian-cancer FDA approved] for patients with [[Ovarian_cancer|epithelial ovarian, fallopian tube, or primary peritoneal cancer]] in combination with [[Carboplatin (Paraplatin)|carboplatin]] and [[Paclitaxel (Taxol)|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)''
+*2018-06-13: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-bevacizumab-combination-chemotherapy-ovarian-cancer FDA approved] for patients with [[Ovarian_cancer|epithelial ovarian, fallopian tube, or primary peritoneal cancer]] in combination with [[Carboplatin (Paraplatin)|carboplatin]] and [[Paclitaxel (Taxol)|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)''
+*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==
-*1/12/2005: Initial market authorization as Avastin.
+*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 staqes III B, III C and IV) [[Ovarian cancer|epithelial ovarian, fallopian tube, or primary peritoneal cancer]].
+*2014-07-31: Extension of indication to include Avastin in combination with paclitaxel, topotecan, or peqylated liposomal doxorubicin for the treatment of adult patients with platinum-resistant recurrent [[Ovarian cancer|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-tarqeted aqents.
+*2015-03-30: Extension of Indication to include treatment of adult patients with persistent, recurrent, or metastatic [[Cervical cancer|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-small cell lung cancer, nonsquamous|non-squamous non-small cell lung cancer (NSCLC)]] with Epidermal Growth Factor Receptor (EGFR) activatinq 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 [[Ovarian cancer|epithelial ovarian, fallopian tube or primary peritoneal cancer]] who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-tarqeted aqents.
+==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|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-small cell lung cancer, nonsquamous|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 [[:Category:High-grade gliomas|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==
@@ Line 95: / Line 122: @@
 [[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:Colon cancer 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:Mesothelioma 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]]
@@ Line 113: / Line 146: @@
 [[Category:Small cell lung cancer medications]]
 [[Category:Testicular cancer medications]]
-[[Category:Endometrial cancer medications]]
+[[Category:Urothelial carcinoma medications]]
-[[Category:Vascular sarcoma medications]]
 [[Category:EMA approved in 2005]]
 [[Category:FDA approved in 2004]]
-[[Category:PMDA approved drugs]]
+[[Category:Health Canada approved in 2005]]
+[[Category:PMDA approved in 2007]]