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{{Short description|Medication}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid [{{fullurl:Bevacizumab|oldid=477061331}} 477061331] of page [[Bevacizumab]] with values updated to verified values.}}
{{Use dmy dates|date=March 2024}}
{{Drugbox
{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug
<!--Monoclonal antibody data-->
| Verifiedfields = changed
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 459978049
| verifiedrevid = 477165031
| type = mab
| type = mab
| image =
| width =
| alt =
| caption =

<!-- Monoclonal antibody data -->
| mab_type = mab
| mab_type = mab
| source = zu/o
| source = zu/o
| target = [[vascular endothelial growth factor A|VEGF-A]]
| target = [[vascular endothelial growth factor A|VEGF-A]]


<!--Clinical data-->
<!--Clinical data-->
| pronounce = {{IPAc-en|ˌ|b|ɛ|v|ə|ˈ|s|ɪ|zj|ʊ|m|æ|b}}<ref name="NIHp">{{cite web | title=Bevacizumab Injection: MedlinePlus Drug Information | url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a607001.html | agency=NLM.nih.gov | date=28 February 2014 | url-status=live | archive-url=https://web.archive.org/web/20140325065239/http://www.nlm.nih.gov/medlineplus/druginfo/meds/a607001.html | archive-date=25 March 2014 }}</ref>
| tradename = Avastin
| tradename = Avastin, others
| Drugs.com = {{drugs.com|monograph|bevacizumab}}
| Drugs.com = {{drugs.com|monograph|bevacizumab}}
| MedlinePlus = a607001
| licence_EU = Avastin
| licence_US = Bevacizumab
| = Bevacizumab
| pregnancy_US = C
| =
| pregnancy_AU_comment = <ref name="Abevmy APM summary">{{cite web | title=Abevmy | website=Therapeutic Goods Administration (TGA) | date=15 September 2021 | url=https://www.tga.gov.au/apm-summary/abevmy | access-date=17 September 2021 | archive-date=16 September 2021 | archive-url=https://web.archive.org/web/20210916174828/https://www.tga.gov.au/apm-summary/abevmy | url-status=live }}</ref><ref name="Drugs.com pregnancy">{{cite web | title=Bevacizumab Use During Pregnancy | website=Drugs.com | date=30 July 2019 | url=https://www.drugs.com/pregnancy/bevacizumab.html | access-date=18 March 2020 | archive-date=18 March 2020 | archive-url=https://web.archive.org/web/20200318210058/https://www.drugs.com/pregnancy/bevacizumab.html | url-status=live }}</ref><ref name="Vegzelma APMDS" />
| legal_status = Rx-only
| pregnancy_category=
| routes_of_administration = [[Intravenous therapy|Intravenous]]
| routes_of_administration = [[Intravenous therapy|Intravenous]], [[intravitreal administration|intravitreal]]
| class =
| ATC_prefix = L01
| ATC_suffix = FG01
| ATC_supplemental = {{ATC|S01|LA08}}
| biosimilars = bevacizumab-adcd,<ref name="Vegzelma FDA label" /> bevacizumab-awwb,<ref name="Mvasi FDA label">{{cite web | title=Mvasi- bevacizumab-awwb injection, solution | website=DailyMed | date=25 June 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0a562b4e-67ce-4bab-852c-d9ee71e55fb8 | access-date=18 March 2020 | archive-date=27 July 2020 | archive-url=https://web.archive.org/web/20200727174041/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0a562b4e-67ce-4bab-852c-d9ee71e55fb8 | url-status=live }}</ref> bevacizumab-bvzr,<ref name="Zirabev FDA label">{{cite web | title=Zirabev- bevacizumab-bvzr injection, solution | website=DailyMed | date=27 January 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa27acbd-d117-4350-aeee-17bc2e2c0ca4 | access-date=18 March 2020 | archive-date=27 July 2020 | archive-url=https://web.archive.org/web/20200727174104/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa27acbd-d117-4350-aeee-17bc2e2c0ca4 | url-status=live }}</ref> bevacizumab-maly,<ref name="Alymsys FDA label">{{cite web | title=Alymsys- bevacizumab-maly injection, solution | website=DailyMed | date=13 April 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6b4040a2-a5c5-4ff0-ab45-935d7e49cf78 | access-date=20 April 2022 | archive-date=10 June 2022 | archive-url=https://web.archive.org/web/20220610024800/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6b4040a2-a5c5-4ff0-ab45-935d7e49cf78 | url-status=live }}</ref> bevacizumab-tnjn, Abevmy,<ref name="Abevmy EPAR" /> Alymsys,<ref name="Alymsys EPAR" /><ref name="Alymsys FDA label" /> Avzivi,<ref name="Avzivi EPAR" /><ref name="Avzivi PI" /> Aybintio,<ref name="Aybintio EPAR" /> Bambevi,<ref name="Bambevi SBD" /> Bevacip,<ref name="AU biosimilar" /> Bevaciptin,<ref name="AU biosimilar" /> Equidacent,<ref name="Equidacent EPAR" /> Mvasi,<ref name="Mvasi EPAR" /> Onbevzi,<ref name="Onbevzi EPAR" /><ref name="Onbevzi APMDS" /> Oyavas,<ref name="Oyavas EPAR" /> Vegzelma,<ref name="Vegzelma FDA label" /><ref name="Vegzelma EPAR" /><ref name="Vegzelma APMDS" /> Zirabev<ref name="Zirabev EPAR" />


<!--Pharmacokinetic data-->
<!-- -->
| legal_AU = S4
| legal_AU_comment = <ref name="Abevmy APM summary" /><ref>{{cite web | title=AusPAR: Bevacizumab | website=Therapeutic Goods Administration (TGA) | date=2 February 2022 | url=https://www.tga.gov.au/resources/auspar/auspar-bevacizumab-6 | access-date=12 June 2022 | archive-date=31 May 2022 | archive-url=https://web.archive.org/web/20220531202916/http://www.tga.gov.au/auspar/auspar-bevacizumab-6 | url-status=live }}</ref><ref name="Vegzelma APMDS">{{cite web | title=Vegzelma APMDS | website=Therapeutic Goods Administration (TGA) | date=18 September 2023 | url=https://www.tga.gov.au/resources/auspmd/vegzelma | access-date=7 March 2024 | archive-date=2 January 2024 | archive-url=https://web.archive.org/web/20240102021205/https://www.tga.gov.au/resources/auspmd/vegzelma | url-status=live }}</ref><ref name="Onbevzi APMDS">{{cite web | title=Onbevzi APMDS | website=Therapeutic Goods Administration (TGA) | date=6 February 2024 | url=https://www.tga.gov.au/resources/auspmd/onbevzi | access-date=7 March 2024 | archive-date=8 February 2024 | archive-url=https://web.archive.org/web/20240208064548/https://www.tga.gov.au/resources/auspmd/onbevzi | url-status=live }}</ref><ref>{{cite web|title=Australian Public Assessment Report for Vegzelma|date=22 February 2024|publisher=[[Department of Health and Aged Care]]|url=https://www.tga.gov.au/sites/default/files/2024-02/auspar-vegzelma-240222.pdf|access-date=18 August 2024}}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = /&nbsp;Schedule D<ref>{{cite web | title=Summary Basis of Decision for Vegzelma | website=[[Health Canada]] | date=2 May 2023 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1684869579695 | access-date=18 June 2023 | archive-date=10 March 2024 | archive-url=https://web.archive.org/web/20240310055559/https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1684869579695 | url-status=live }}</ref><ref>{{cite web | title=Vegzelma Product information | website=[[Health Canada]] | date=3 January 2023 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=102312 | access-date=18 June 2023 | archive-date=10 March 2024 | archive-url=https://web.archive.org/web/20240310055437/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=102312 | url-status=live }}</ref><ref>{{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=[[Health Canada]] | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024}}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment = <ref name="Avastin FDA label" /><ref name="Mvasi FDA label" /><ref name="Zirabev FDA label" /><ref name="Alymsys FDA label" /><ref name="Vegzelma FDA label" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Avastin EPAR" /><ref name="Mvasi EPAR" /><ref name="Zirabev EPAR" /><ref name="Aybintio EPAR" /><ref name="Equidacent EPAR" /><ref name="Alymsys EPAR" /><ref name="Onbevzi EPAR" /><ref name="Abevmy EPAR" /><ref name="Oyavas EPAR" /><ref name="Vegzelma EPAR" />
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status = Rx-only

<!-- Pharmacokinetic data -->
| bioavailability = 100% (IV only)
| bioavailability = 100% (IV only)
| protein_bound =
| metabolism =
| metabolites =
| onset =
| elimination_half-life = 20 days (range: 11–50 days)
| elimination_half-life = 20 days (range: 11–50 days)
| duration_of_action =
| excretion =


<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 216974-75-3
| CAS_number = 216974-75-3
| CAS_supplemental =
| ATC_prefix = L01
| PubChem =
| ATC_suffix = XC07
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00112
| DrugBank = DB00112
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2S9ZZM9Q9V
| UNII = 2S9ZZM9Q9V
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D06409
| KEGG = D06409
| ChEBI_Ref =
| ChEBI =
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = <!-- blanked - oldvalue: 1201583 -->
| ChEMBL = 1201583
| NIAID_ChemDB =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| PDB_ligand =
| ChemSpiderID = NA
| synonyms = bevacizumab gamma


<!--Chemical data-->
<!--Chemical data-->
| C=6638 | H=10160 | N=1720 | O=2108 | S=44
| C=6638 | H=10160 | N=1720 | O=2108 | S=44
| SMILES =
| molecular_weight = approx. 149 [[kDa]]
| StdInChI =
| StdInChI_comment =
| StdInChIKey =
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
}}

<!-- Definition and medical uses -->
'''Bevacizumab''', sold under the brand name '''Avastin''' among others, is a [[monoclonal antibody]] medication used to treat a number of types of [[cancer]]s and a specific [[eye disease]].<ref name=AHFS2016/><ref name="Avastin FDA label">{{cite web | title=Avastin- bevacizumab injection, solution | website=DailyMed | date=28 June 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=939b5d1f-9fb2-4499-80ef-0607aa6b114e | access-date=18 March 2020 | archive-date=27 July 2020 | archive-url=https://web.archive.org/web/20200727174050/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=939b5d1f-9fb2-4499-80ef-0607aa6b114e | url-status=live }}</ref> For cancer, it is given by slow injection into a vein ([[Intravenous therapy|intravenous]]) and used for [[colon cancer]], [[lung cancer]], [[ovarian cancer]], [[glioblastoma]], [[hepatocellular carcinoma]], and [[renal cell carcinoma|renal-cell carcinoma]].<ref>{{cite web | title=Bevacizumab | website=National Cancer Institute | date=5 October 2006 | url=https://www.cancer.gov/about-cancer/treatment/drugs/bevacizumab | access-date=22 December 2023 | archive-date=10 April 2020 | archive-url=https://web.archive.org/web/20200410064746/https://www.cancer.gov/about-cancer/treatment/drugs/bevacizumab | url-status=live }}</ref> In many of these diseases it is used as a [[first-line therapy]].<ref name=AHFS2016/><ref name="Avastin FDA label" /> For [[age-related macular degeneration]] it is given by injection into the eye ([[Intravitreal injection|intravitreal]]).<ref name=AHFS2016/>

<!-- Side effects and mechanism -->
Common side effects when used for cancer include [[nose bleeds]], headache, high blood pressure, and rash.<ref name=AHFS2016/> Other severe side effects include [[gastrointestinal perforation]], bleeding, [[allergic reactions]], [[blood clots]], and an increased risk of infection.<ref name=AHFS2016/> When used for eye disease side effects can include [[vision loss]] and [[retinal detachment]].<ref name=AHFS2016/> Bevacizumab is a monoclonal antibody that functions as an [[angiogenesis inhibitor]].<ref name=AHFS2016/> It works by slowing the [[angiogenesis|growth of new blood vessels]] by inhibiting [[vascular endothelial growth factor A]] (VEGF-A), in other words [[Anti–vascular endothelial growth factor therapy|anti–VEGF therapy]].<ref name=AHFS2016/>

<!-- History and culture -->
Bevacizumab was approved for medical use in the United States in 2004.<ref>{{cite web | title=Drug Approval Package: Avastin (Bevacizum) NDA #125085 | website=U.S. [[Food and Drug Administration]] (FDA) | date=8 March 2005 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/STN-125085_Avastin.cfm | access-date=29 December 2021 | archive-date=8 April 2021 | archive-url=https://web.archive.org/web/20210408212614/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/STN-125085_Avastin.cfm | url-status=live }}</ref><ref name=AHFS2016>{{cite web|title=Bevacizumab|url=https://www.drugs.com/monograph/bevacizumab.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220192620/https://www.drugs.com/monograph/bevacizumab.html|archive-date=20 December 2016}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref>

==Medical uses==

=== Colorectal cancer ===
Bevacizumab was approved in the United States in February 2004, for use in metastatic [[colorectal cancer]] when used with standard chemotherapy treatment (as [[first-line treatment]]).<ref name=":1">{{cite journal | vauthors = Cohen MH, Gootenberg J, Keegan P, Pazdur R | title = FDA drug approval summary: bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer | journal = The Oncologist | volume = 12 | issue = 3 | pages = 356–61 | date = March 2007 | pmid = 17405901 | doi = 10.1634/theoncologist.12-3-356 | s2cid = 21241228 | doi-access = free }}</ref> In June 2006, it was approved with 5-fluorouracil-based therapy for second-line metastatic colorectal cancer.<ref name=":1" />

It was approved by the [[European Medicines Agency]] (EMA) in January 2005, for use in [[colorectal cancer]].<ref name="EMA_2005" /><ref name="Avastin EPAR">{{cite web | title=Avastin EPAR | website=[[European Medicines Agency]] (EMA) | date=11 March 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/avastin | access-date=18 March 2020 | archive-date=18 March 2020 | archive-url=https://web.archive.org/web/20200318210110/https://www.ema.europa.eu/en/medicines/human/EPAR/avastin | url-status=live }}</ref>

Bevacizumab has also been examined as an add on to other chemotherapy drugs in people with non-metastatic colon cancer. The data from two large randomized studies showed no benefit in preventing the cancer from returning and a potential to cause harm in this setting.<ref>{{cite journal | vauthors = Van Cutsem E, Lambrechts D, Prenen H, Jain RK, Carmeliet P | title = Lessons from the adjuvant bevacizumab trial on colon cancer: what next? | journal = Journal of Clinical Oncology | volume = 29 | issue = 1 | pages = 1–4 | date = January 2011 | pmid = 21115866 | doi = 10.1200/JCO.2010.32.2701 | doi-access = free }}</ref>

In the EU, bevacizumab in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of adults with metastatic carcinoma of the colon or rectum.<ref name="Equidacent EPAR" />

=== Lung cancer ===
In 2006, the US [[Food and Drug Administration]] (FDA) approved bevacizumab for use in [[first-line therapy|first-line]] advanced nonsquamous [[Non-small-cell lung carcinoma|non-small cell lung cancer]] in combination with carboplatin/paclitaxel chemotherapy. The approval was based on the pivotal study E4599 (conducted by the Eastern Cooperative Oncology Group), which demonstrated a two-month improvement in overall survival in patients treated with bevacizumab (Sandler, et al. NEJM 2004).{{Citation needed|date=January 2021}} A preplanned analysis of histology in E4599 demonstrated a four-month median survival benefit with bevacizumab for people with adenocarcinoma (Sandler, et al. JTO 2010);{{Citation needed|date=January 2021}} adenocarcinoma represents approximately 85% of all non-squamous cell carcinomas of the lung.

A subsequent European clinical trial, AVAiL, was first reported in 2009 and confirmed the significant improvement in progression-free survival shown in E4599 (Reck, et al. Ann. Oncol. 2010).{{Citation needed|date=January 2021}} An overall survival benefit was not demonstrated in patients treated with bevacizumab; however, this may be due to the more limited use of bevacizumab as maintenance treatment in AVAiL versus E4599 (this differential effect is also apparent in the European vs US trials of bevacizumab in colorectal cancer: Tyagi and Grothey, Clin Colorectal Cancer, 2006).{{Citation needed|date=January 2021}} As an anti-angiogenic agent, there is no mechanistic rationale for stopping bevacizumab before disease progression. Stated another way, the survival benefits achieved with bevacizumab can only be expected when used in accordance with the clinical evidence: continued until disease progression or treatment-limiting side effects.

Another large European-based clinical trial with bevacizumab in lung cancer, AVAPERL, was reported in October 2011 (Barlesi, et al. ECCM 2011).{{Citation needed|date=January 2021}} First-line patients were treated with bevacizumab plus cisplatin/pemetrexed for four cycles, and then randomized to receive maintenance treatment with either bevacizumab/pemetrexed or bevacizumab alone until disease progression. Maintenance treatment with bevacizumab/pemetrexed demonstrated a 50% reduction in risk of progression vs bevacizumab alone (median PFS: 10.2 vs 6.6 months). Maintenance treatment with bevacizumab/pemetrexed did not confer a significant increase in overall survival vs bevacizumab alone on follow up analysis.<ref>{{cite journal | vauthors = Barlesi F, Scherpereel A, Gorbunova V, Gervais R, Vikström A, Chouaid C, Chella A, Kim JH, Ahn MJ, Reck M, Pazzola A, Kim HT, Aerts JG, Morando C, Loundou A, Groen HJ, Rittmeyer A | title = Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous nonsmall-cell lung cancer: updated survival analysis of the AVAPERL (MO22089) randomized phase III trial | journal = Annals of Oncology | volume = 25 | issue = 5 | pages = 1044–52 | date = May 2014 | pmid = 24585722 | doi = 10.1093/annonc/mdu098 | doi-access = free }}</ref>

In the EU, bevacizumab, in addition to platinum-based chemotherapy, is indicated for first-line treatment of adults with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology.<ref name="Equidacent EPAR" /> Bevacizumab, in combination with erlotinib, is indicated for first-line treatment of adults with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations.<ref name="Equidacent EPAR" />

=== Breast cancer ===
In December 2010, the US [[Food and Drug Administration]] (FDA) notified its intention to remove the breast cancer indication from bevacizumab, saying that it had not been shown to be safe and effective in [[breast cancer]] patients.<ref>{{cite web | title=Questions and Answers about Avastin | website=U.S. [[Food and Drug Administration]] (FDA) | date=16 December 2010 | url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questions-and-answers-about-avastin | access-date=22 April 2020 | archive-date=23 April 2020 | archive-url=https://web.archive.org/web/20200423031304/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questions-and-answers-about-avastin | url-status=live }}</ref><ref>{{cite web | title=Avastin (bevacizumab) Information | website=U.S. [[Food and Drug Administration]] (FDA) | date=29 June 2011 | url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/avastin-bevacizumab-information | access-date=22 April 2020 | archive-date=23 April 2020 | archive-url=https://web.archive.org/web/20200423031612/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/avastin-bevacizumab-information | url-status=live }}</ref> The combined data from four different clinical trials showed that bevacizumab neither prolonged overall survival nor slowed disease progression sufficiently to outweigh the risk it presents to patients. This only prevented Genentech from marketing bevacizumab for breast cancer. Doctors are free to prescribe bevacizumab [[Off-label use|off label]], although insurance companies are less likely to approve off-label treatments.<ref name="FDA breast1">{{cite press release | title=FDA begins process to remove breast cancer indication from Avastin label | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=16 December 2010 | url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm237172.htm | access-date=17 December 2010 | url-status=dead | archive-url=https://web.archive.org/web/20101216181330/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm237172.htm | archive-date=16 December 2010 }}</ref><ref name="Breast Cancer">{{cite news |url= https://www.nytimes.com/2010/12/17/health/policy/17drug.html |title=F.D.A. Rejects Use of Drug in Cases of Breast Cancer |newspaper=[[The New York Times]] |date=16 December 2010 |access-date=16 December 2010| vauthors = Andrew P |url-status=live |archive-url= https://web.archive.org/web/20121111072830/http://www.nytimes.com/2010/12/17/health/policy/17drug.html |archive-date= 11 November 2012}}</ref> In June 2011, an FDA panel unanimously rejected an appeal by Roche. A panel of cancer experts ruled for a second time that Avastin should no longer be used in breast cancer patients, clearing the way for the US government to remove its endorsement from the drug. The June 2011 meeting of the FDA's oncologic drug advisory committee was the last step in an appeal by the drug's maker. The committee concluded that breast cancer clinical studies of patients taking Avastin have shown no advantage in survival rates, no improvement in quality of life, and significant side effects.<ref name=scijul11>{{cite journal | vauthors = Couzin-Frankel J, Ogale Y | title = FDA. Once on 'fast track,' avastin now derailed | journal = Science | volume = 333 | issue = 6039 | pages = 143–4 | date = July 2011 | pmid = 21737712 | doi = 10.1126/science.333.6039.143 }}</ref>

In the EU, bevacizumab in combination with paclitaxel is indicated for [[first-line treatment]] of adults with metastatic breast cancer.<ref name="Equidacent EPAR" /> Bevacizumab in combination with capecitabine is indicated for first-line treatment of adults with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate.<ref name="Equidacent EPAR" />

=== Kidney cancer ===
In certain kidney cancers, bevacizumab improves the progression free survival time but not survival time. In 2009, the FDA approved bevacizumab for use in metastatic [[renal cell carcinoma|renal cell cancer]] (a form of [[kidney cancer]]).<ref>{{cite news |title=FDA clears Genentech drug for kidney cancer |newspaper=[[San Francisco Chronicle]] |date=2 August 2009 |url=http://www.sfgate.com/cgi-bin/article.cgi?f=/n/a/2009/08/02/financial/f190253D65.DTL |url-status=dead |archive-url=https://web.archive.org/web/20100930173358/http://www.sfgate.com/cgi-bin/article.cgi?f=%2Fn%2Fa%2F2009%2F08%2F02%2Ffinancial%2Ff190253D65.DTL |archive-date=30 September 2010 }}</ref><ref>{{cite web |url=http://www.genengnews.com/news/bnitem.aspx?name=59562374 |title=FDA Gives Roche's Avastin the Go-Ahead for Metastatic Renal Carcinoma |publisher=Genetic Engineering & Biotechnology News |work=GENNewsHighlights |date=3 August 2009 |access-date=13 August 2012 |archive-date=11 May 2020 |archive-url=https://web.archive.org/web/20200511104403/https://www.genengnews.com/news/bnitem.aspx?name=59562374 |url-status=live }}</ref> following earlier reports of activity<ref>{{cite journal | vauthors = Rini BI | title = Vascular endothelial growth factor-targeted therapy in renal cell carcinoma: current status and future directions | journal = Clinical Cancer Research | volume = 13 | issue = 4 | pages = 1098–106 | date = February 2007 | pmid = 17317817 | doi = 10.1158/1078-0432.CCR-06-1989 | doi-access = free }}</ref> EU approval was granted in 2007.<ref>{{cite web|last=European Medicines Agency|date=January 2008|title=Avastin-H-C-582-II-0015 : EPAR - Assessment Report - Variation |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000582/WC500029268.pdf|url-status=live|archive-url=https://web.archive.org/web/20120130051258/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000582/WC500029268.pdf|archive-date=30 January 2012}}</ref>

In the EU, bevacizumab in combination with interferon alfa-2a is indicated for [[first-line treatment]] of adults with advanced and/or metastatic renal cell cancer.<ref name="Equidacent EPAR" />

===Brain cancers===
Bevacizumab slows tumor growth but does not affect overall survival in people with [[glioblastoma]].<ref name=Am2018>{{cite journal | vauthors = Ameratunga M, Pavlakis N, Wheeler H, Grant R, Simes J, Khasraw M | title = Anti-angiogenic therapy for high-grade glioma | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | pages = CD008218 | date = November 2018 | issue = 11 | pmid = 30480778 | pmc = 6516839 | doi = 10.1002/14651858.CD008218.pub4 }}</ref> The FDA granted [[accelerated approval]] for the treatment of recurrent [[glioblastoma multiforme]] in May 2009.<ref>{{cite web| url=http://www.cancer.gov/cancertopics/druginfo/fda-bevacizumab#Anchor-Glioblastoma| title=FDA Approval for Bevacizumab| vauthors = Richard P | publisher=National Cancer Institute| access-date=11 May 2010| date=May 2009| url-status=dead| archive-url= https://web.archive.org/web/20100110061727/http://www.cancer.gov/cancertopics/druginfo/fda-bevacizumab#Anchor-Glioblastoma | archive-date=10 January 2010}}</ref><ref>{{cite web | title=FDA Grants Accelerated Approval of Avastin for Brain Cancer (Glioblastoma) That Has Progressed Following Prior Therapy | website=Drugs.com | date=5 May 2009 | url=https://www.drugs.com/newdrugs/fda-grants-accelerated-approval-avastin-brain-cancer-glioblastoma-has-progressed-following-prior-1342.html | access-date=22 April 2020 | archive-date=26 July 2020 | archive-url=https://web.archive.org/web/20200726225325/https://www.drugs.com/newdrugs/fda-grants-accelerated-approval-avastin-brain-cancer-glioblastoma-has-progressed-following-prior-1342.html | url-status=live }}</ref> A 2018 Cochrane review deemed there to not be good evidence for its use in recurrences either.<ref name=Am2018/>

===Macular degeneration ===
In the EU, bevacizumab gamma (Lytenava) is indicated for the treatment of neovascular (wet) age-related macular degeneration (nAMD).<ref name="Lytenava EPAR" />

=== Ovarian cancer ===
In 2018, the US [[Food and Drug Administration]] (FDA) approved bevacizumab in combination with [[chemotherapy]] for stage III or IV of [[ovarian cancer]] after initial surgical operation, followed by single-agent bevacizumab. The approval was based on a study of the addition of bevacizumab to [[carboplatin]] and [[paclitaxel]].<ref name="FDA-ovarian cancer">{{cite web |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-bevacizumab-combination-chemotherapy-ovarian-cancer |title=FDA approves bevacizumab in combination with chemotherapy for ovarian cancer |date=13 June 2018 |website=U.S. [[Food and Drug Administration]] (FDA) |access-date=4 August 2018 |archive-date=18 March 2020 |archive-url=https://web.archive.org/web/20200318201628/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-bevacizumab-combination-chemotherapy-ovarian-cancer |url-status=live }} {{PD-notice}}</ref> Progression-free survival was increased to 18 months from 13 months.<ref name="FDA-ovarian cancer"/>

In the EU, bevacizumab, in combination with carboplatin and paclitaxel is indicated for the front-line treatment of adults with advanced (International Federation of Gynecology and Obstetrics (FIGO) stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.<ref name="Equidacent EPAR" /> Bevacizumab, in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel, is indicated for treatment of adults 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.<ref name="Equidacent EPAR" />

In May 2020, the FDA expanded the indication of [[olaparib]] to include its combination with bevacizumab for first-line maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability.<ref>{{cite press release | title=FDA approves olaparib plus bevacizumab as maintenance treatment for ovarian, fallopian tube, or primary peritoneal cancers | website=U.S. [[Food and Drug Administration]] (FDA) | date=8 May 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-plus-bevacizumab-maintenance-treatment-ovarian-fallopian-tube-or-primary | access-date=12 October 2020 | archive-date=26 October 2020 | archive-url=https://web.archive.org/web/20201026161721/https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-plus-bevacizumab-maintenance-treatment-ovarian-fallopian-tube-or-primary | url-status=live }} {{PD-notice}}</ref>

=== Cervical cancer ===
In the EU, bevacizumab, in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in people who cannot receive platinum therapy, is indicated for the treatment of adults with persistent, recurrent, or metastatic carcinoma of the cervix.<ref name="Equidacent EPAR" />

==Adverse effects==
Bevacizumab inhibits the growth of blood vessels, which is part of the body's normal healing and maintenance. The body grows new blood vessels in [[wound healing]], and as [[collateral circulation]] around blocked or [[atherosclerosis|atherosclerotic]] blood vessels. One concern is that bevacizumab will interfere with these normal processes, and worsen conditions like [[coronary artery disease]] or [[peripheral artery disease]].<ref>{{cite journal | vauthors = Semenza GL | title = A new weapon for attacking tumor blood vessels | journal = The New England Journal of Medicine | volume = 358 | issue = 19 | pages = 2066–7 | date = May 2008 | pmid = 18463385 | doi = 10.1056/NEJMcibr0800272 }}</ref>

The main side effects are [[hypertension]] and heightened risk of [[bleeding]]. [[Bowel perforation]] has been reported.<ref>{{cite journal | vauthors = Sliesoraitis S, Tawfik B | title = Bevacizumab-induced bowel perforation | journal = The Journal of the American Osteopathic Association | volume = 111 | issue = 7 | pages = 437–41 | date = July 2011 | pmid = 21803880 }}</ref> Fatigue and infection are also common.<ref>{{cite web |url=http://www.gene.com/download/pdf/avastin_prescribing.pdf |title = AVASTIN (bevacizumab) injection, for intravenous use | publisher = Genentech, Inc. |access-date=2 June 2016 |url-status=live |archive-url=https://web.archive.org/web/20160429054035/http://www.gene.com/download/pdf/avastin_prescribing.pdf |archive-date=29 April 2016 }}</ref>

In advanced lung cancer, less than half of patients qualify for treatment.<ref>{{cite journal | vauthors = Velcheti V, Viswanathan A, Govindan R | title = The proportion of patients with metastatic non-small cell lung cancer potentially eligible for treatment with bevacizumab: a single institutional survey | journal = Journal of Thoracic Oncology | volume = 1 | issue = 5 | pages = 501 | date = June 2006 | pmid = 17409907 | doi = 10.1097/01243894-200606000-00023 | doi-broken-date = 7 September 2024 }}</ref><ref>{{cite journal | vauthors = Vaughn C, Zhang L, Schiff D | title = Reversible posterior leukoencephalopathy syndrome in cancer | journal = Current Oncology Reports | volume = 10 | issue = 1 | pages = 86–91 | date = January 2008 | pmid = 18366965 | doi = 10.1007/s11912-008-0013-z | s2cid = 40332552 }}</ref> [[Nasal septum perforation]] and renal [[thrombotic microangiopathy]] have been reported.<ref>{{cite journal | vauthors = Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, Richardson C, Kopp JB, Kabir MG, Backx PH, Gerber HP, Ferrara N, Barisoni L, Alpers CE, Quaggin SE | title = VEGF inhibition and renal thrombotic microangiopathy | journal = The New England Journal of Medicine | volume = 358 | issue = 11 | pages = 1129–36 | date = March 2008 | pmid = 18337603 | pmc = 3030578 | doi = 10.1056/NEJMoa0707330 }}</ref> In December 2010, the FDA warned of the risk of developing perforations in the body, including in the nose, stomach, and intestines.

In 2013, Hoffmann-La Roche announced that the drug was associated with 52 cases of [[necrotizing fasciitis]] from 1997 to 2012, of which 17 patients died.<ref>{{cite news|url=https://www.cbc.ca/news/health/cancer-drug-avastin-tied-to-2-cases-of-flesh-eating-disease-in-canada-1.1365843|title=Cancer drug Avastin tied to 2 cases of flesh-eating disease in Canada|publisher=[[CBC News]]|date=2 May 2013|access-date=2 May 2013|url-status=live|archive-url=https://web.archive.org/web/20130502173839/http://www.cbc.ca/news/health/story/2013/05/02/avastin-flesh-eating-disease.html|archive-date=2 May 2013}}</ref> About 2/3 of cases involved patients with [[colorectal cancer]], or patients with [[gastrointestinal perforation]]s or [[fistula]]s.

These effects are largely avoided in [[Ophthalmology|ophthalmological]] use since the drug is introduced directly into the eye thus minimizing any effects on the rest of the body.{{Citation needed|date=July 2011}}

Neurological adverse events include [[Posterior reversible encephalopathy syndrome|reversible posterior encephalopathy syndrome]]. Ischemic and hemorrhagic strokes are also possible.<ref>{{cite journal | vauthors = Godfrey SE | title = Estrogen receptors | journal = American Journal of Clinical Pathology | volume = 91 | issue = 5 | pages = 629–30 | date = May 1989 | doi = 10.1215/15228517-2008-118 | pmid = 2718965 | pmc = 2718965 }}</ref>

[[Proteinuria|Protein in the urine]] occurs in approximately 20% of people. This does not require permanent discontinuation of the drug. Nonetheless, the presence of [[nephrotic syndrome]] necessitates permanent discontinuation of bevacizumab.<ref name="PrescribingInformation" />

==Mechanism of action==
Bevacizumab is a recombinant humanized [[monoclonal antibody]] that blocks angiogenesis by inhibiting [[vascular endothelial growth factor A]] (VEGF-A).<ref name=Los>{{cite journal | vauthors = Los M, Roodhart JM, Voest EE | title = Target practice: lessons from phase III trials with bevacizumab and vatalanib in the treatment of advanced colorectal cancer | journal = The Oncologist | volume = 12 | issue = 4 | pages = 443–50 | date = April 2007 | pmid = 17470687 | doi = 10.1634/theoncologist.12-4-443 | doi-access = free }}</ref> VEGF-A is a growth factor protein that stimulates angiogenesis in a variety of diseases, especially in [[cancer]]. By binding VEGF-A, bevacizumab should act outside the cell, but in some cases (cervical and breast cancer) it is taken up by cells through constitutive endocytosis.<ref>{{cite journal | vauthors = Karpinska A, Magiera G, Kwapiszewska K, Hołyst R |title=Cellular Uptake of Bevacizumab in Cervical and Breast Cancer Cells Revealed by Single-Molecule Spectroscopy |journal=Journal of Physical Chemistry Letters |date=2023 |volume=14 |issue=5 |pages=1272–1278 |doi=10.1021/acs.jpclett.2c03590|pmid=36719904 |pmc=9923738 }}</ref> It also is taken up by retinal photoreceptor cells after intravitreal injection.<ref name="pmid17525217">{{cite journal | vauthors = Heiduschka P, Fietz H, Hofmeister S, Schultheiss S, Mack AF, Peters S, Ziemssen F, Niggemann B, Julien S, Bartz-Schmidt KU, Schraermeyer U | title = Penetration of bevacizumab through the retina after intravitreal injection in the monkey | journal = Investigative Ophthalmology & Visual Science | volume = 48 | issue = 6 | pages = 2814–23 | date = June 2007 | pmid = 17525217 | doi = 10.1167/iovs.06-1171 }}</ref>

==Chemistry==

Bevacizumab was originally derived from a mouse monoclonal antibody generated from mice immunized with the 165-residue form of recombinant human vascular endothelial growth factor. It was humanized by retaining the [[complementarity-determining region|binding region]] and replacing the rest with a human full [[Immunoglobulin light chain|light chain]] and a human truncated IgG1 [[Immunoglobulin heavy chain|heavy chain]], with some other substitutions. The resulting plasmid was transfected into [[Chinese hamster ovary cell]]s which are grown in [[industrial fermentation]] systems.<ref name="EMA_2005">{{cite web | work = European Medicines Agency | date = 2005 | url = http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000582/WC500029262.pdf | title = Bevacizumab Scientific Discussion | archive-url = https://web.archive.org/web/20150924012014/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000582/WC500029262.pdf | archive-date = 24 September 2015 }}</ref>{{rp|4}}

==History==

Bevacizumab is a [[recombinant protein|recombinant]] humanized [[monoclonal antibody]] and in 2004, it became the first clinically used angiogenesis inhibitor.<ref name=NYT2004>{{cite web | vauthors = Pollack A | work = The New York Times | date = 27 February 2004 | url = https://www.nytimes.com/2004/02/27/business/fda-approves-cancer-drug-from-genentech.html | title = F.D.A. Approves Cancer Drug From Genentech | archive-url = https://web.archive.org/web/20161024050313/http://www.nytimes.com/2004/02/27/business/fda-approves-cancer-drug-from-genentech.html | archive-date=24 October 2016 }}</ref> Its development was based on the discovery of human [[vascular endothelial growth factor]] (VEGF), a protein that stimulated blood vessel growth, in the laboratory of [[Genentech]] scientist [[Napoleone Ferrara]].<ref>{{cite journal | vauthors = Palmer AM, Stephenson FA, Williams RJ | title = Society for Medicines Research: 40th anniversary symposium | journal = Drug News & Perspectives | volume = 20 | issue = 3 | pages = 191–6 | date = April 2007 | pmid = 17520096 }}</ref><ref>{{cite journal | vauthors = Ferrara N | title = Anti-angiogenic drugs to treat human disease: an interview with Napoleone Ferrara by Kristin H. Kain | journal = Disease Models & Mechanisms | volume = 2 | issue = 7–8 | pages = 324–5 | year = 2009 | pmid = 19553691 | doi = 10.1242/dmm.002972 | s2cid = 22035397 | doi-access = }}</ref><ref name=Saga>{{cite journal | vauthors = Ribatti D | title = Napoleone Ferrara and the saga of vascular endothelial growth factor | journal = Endothelium | volume = 15 | issue = 1 | pages = 1–8 | year = 2008 | pmid = 18568940 | doi = 10.1080/10623320802092377 }}</ref> Ferrara later demonstrated that antibodies against VEGF inhibit tumor growth in mice.<ref>{{cite journal | vauthors = Ferrara N | title = From the discovery of vascular endothelial growth factor to the introduction of avastin in clinical trials - an interview with Napoleone Ferrara by Domenico Ribatti | journal = The International Journal of Developmental Biology | volume = 55 | issue = 4–5 | pages = 383–8 | year = 2011 | pmid = 21858763 | doi = 10.1387/ijdb.103216dr | doi-access = free }}</ref> His work validated the hypothesis of [[Judah Folkman]], proposed in 1971, that stopping angiogenesis might be useful in controlling cancer growth.<ref name=Saga/>

===Approval===
It received its first approval in the United States in 2004, for combination use with standard [[chemotherapy]] for metastatic [[colon cancer]].<ref name=PrescribingInformation>{{cite web |title=Avastin full Prescribing Information - Genentech |url=http://www.gene.com/gene/products/information/pdf/avastin-prescribing.pdf |agency=Gene.com |date=2011 |url-status=live |archive-url=https://web.archive.org/web/20110714110417/http://www.gene.com/gene/products/information/pdf/avastin-prescribing.pdf |archive-date=14 July 2011 }}</ref> It has since been approved for use in certain lung cancers, renal cancers, ovarian cancers, and [[glioblastoma multiforme]] of the brain.{{medcn|date=January 2020}}

In 2008, bevacizumab was approved for [[breast cancer]] by the FDA, but the approval was revoked on 18 November 2011<ref name=BreastFDA>{{cite web |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm280536.htm |title=Press Announcements - FDA Commissioner announces Avastin decision |date=18 November 2011 |website=U.S. Food and Drug Administration |access-date=31 October 2014 |url-status=live |archive-url=https://web.archive.org/web/20141215150605/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm280536.htm |archive-date=15 December 2014 }}</ref><ref name="NYT2011">{{cite news | vauthors = Pollack A |title=F.D.A. Revokes Approval of Avastin for Breast Cancer |newspaper=The New York Times |date=18 November 2011 |url=http://prescriptions.blogs.nytimes.com/2011/11/18/f-d-a-revokes-approval-of-avastin-for-breast-cancer/ |url-status=live |archive-url=https://web.archive.org/web/20111121024826/http://prescriptions.blogs.nytimes.com/2011/11/18/f-d-a-revokes-approval-of-avastin-for-breast-cancer/ |archive-date=21 November 2011 }}</ref><ref name="bbc">{{cite news|url=https://www.bbc.co.uk/news/world-us-canada-15800907|title=Cancer drug Avastin loses US approval|work=[[BBC News Online]]|date=18 November 2011|url-status=live|archive-url=https://web.archive.org/web/20111119133043/http://www.bbc.co.uk/news/world-us-canada-15800907|archive-date=19 November 2011}}</ref> because, although there was evidence that it slowed progression of metastatic breast cancer, there was no evidence that it extended life or improved quality of life, and it caused adverse effects including severe high blood pressure and hemorrhaging.{{medcn|date=August 2022}}

In 2008, the FDA gave bevacizumab provisional approval for metastatic breast cancer, subject to further studies. The FDA's advisory panel had recommended against approval.<ref name=nytimesref>{{cite news |url=https://www.nytimes.com/2008/02/22/business/apee-drug.html |title=F.D.A. Approves Drug's Use for Breast Cancer |work=[[The New York Times]] |date=22 February 2008 |url-status=live |archive-url=https://web.archive.org/web/20170202064944/http://www.nytimes.com/2008/02/22/business/apee-drug.html |archive-date=2 February 2017 }}</ref> In July 2010, after new studies failed to show a significant benefit, the FDA's advisory panel recommended against the indication for advanced breast cancer. Genentech requested a hearing, which was granted in June 2011. The FDA ruled to withdraw the breast cancer indication in November 2011. FDA approval is required for Genentech to market a drug for that indication. Doctors may sometimes prescribe it for that indication, although insurance companies are less likely to pay for it.<ref name="NYT2011"/>

The drug remains approved for breast cancer use in other countries, including Australia.<ref>{{cite news |url=http://www.abc.net.au/news/stories/2010/07/22/2960728.htm |title=Breast cancer drug 'still safe' for Aussie women |agency=[[Australian Broadcasting Corporation]] |date=22 July 2010 |url-status=live |archive-url=https://web.archive.org/web/20100723132712/http://www.abc.net.au/news/stories/2010/07/22/2960728.htm |archive-date=23 July 2010 }}</ref> It has been funded by the English NHS [[Cancer Drugs Fund]], but in January 2015 it was proposed to remove it from the approved list.<ref>{{cite news|title=David Cameron's flagship Cancer Drugs Fund 'is a waste of NHS cash'|url=https://www.theguardian.com/politics/2015/jan/10/cancer-drugs-fund-waste-of-nhs-cash-david-cameron|access-date=11 January 2015|newspaper=[[The Guardian]]|date=10 January 2015|url-status=live|archive-url=https://web.archive.org/web/20150115065953/http://www.theguardian.com/politics/2015/jan/10/cancer-drugs-fund-waste-of-nhs-cash-david-cameron|archive-date=15 January 2015}}</ref> It remains on the Cancer Drugs Fund as of March 2023.<ref>{{cite web |title=NHS England » National Cancer Drugs Fund list |url=https://www.england.nhs.uk/publication/national-cancer-drugs-fund-list/ |access-date=9 March 2023 |website=www.england.nhs.uk |archive-date=9 March 2023 |archive-url=https://web.archive.org/web/20230309153610/https://www.england.nhs.uk/publication/national-cancer-drugs-fund-list/ |url-status=live }}</ref>

==Society and culture==

===Use for macular degeneration===

In 2015, there was a fierce debate in the UK and other European countries concerning the choice of prescribing bevacizumab or [[ranibizumab]] (Lucentis) for wet AMD.<ref name=BMJ2015pt1>{{cite news|title=Why have UK doctors been deterred from prescribing Avastin?|url=http://www.bmj.com/content/350/bmj.h1654|publisher=The British Medical Journal|date=1 April 2015|access-date=2 April 2015|archive-date=4 April 2015|archive-url=https://web.archive.org/web/20150404232028/http://www.bmj.com/content/350/bmj.h1654|url-status=live}}</ref> In the UK, part of the tension was between on the one hand, both the [[European Medicines Agency]] and the [[Medicines and Healthcare products Regulatory Agency]] which had approved Lucentis but not Avastin for wet AMD, and their interest in ensuring that doctors do not use medicines off-label when there are other, approved medications for the same indication, and on the other hand, [[NICE]] in the UK, which sets treatment guidelines, and has been unable so far to appraise Avastin as a first-line treatment, in order to save money for the [[National Health Service]].<ref name=BMJ2015pt1/> Novartis and Roche (which respectively have marketing rights and ownership rights for Avastin) had not conducted clinical trials to get approval for Avastin for wet AMD and had no intention of doing so.<ref name=BMJ2015pt1/> Further, both companies lobbied against treatment guidelines that would make Avastin a first-line treatment, and when government-funded studies comparing the two drugs were published, they published papers emphasizing the risks of using Avastin for wet AMD.<ref name=BMJ2015pt1/>

In March 2024, the [[Committee for Medicinal Products for Human Use]] (CHMP) of the [[European Medicines Agency]] (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Lytenava (bevacizumab gamma), intended for treatment of neovascular (wet) age-related macular degeneration (nAMD).<ref name="Lytenava EPAR" /><ref>{{cite press release | title=Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 18-21 March 2024 | website=European Medicines Agency | date=22 March 2024 | url=https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-18-21-march-2024 | access-date=13 June 2024}}</ref> The applicant for this medicinal product is Outlook Therapeutics Limited.<ref name="Lytenava EPAR">{{cite web | title=Lytenava EPAR | website=European Medicines Agency | date=21 March 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lytenava | access-date=23 March 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Lytenava was approved for medical use in the European Union in May 2024.<ref name="Lytenava EPAR" />

=== Breast cancer approval ===
In March 2007, the European Commission approved bevacizumab in combination with [[paclitaxel]] for the first-line treatment of metastatic breast cancer.<ref name="Austria-Codex">{{cite book |title=Austria-Codex |publisher=Österreichischer Apothekerverlag |year=2007 |isbn=978-3-85200-181-4 | veditors = Jasek W |edition=2007/2008 |location=Vienna |language=de }}{{Page needed|date=July 2011}}</ref>

In 2008, the FDA approved bevacizumab for use in [[breast cancer]]. A panel of outside advisers voted 5 to 4 against approval, but their recommendations were overruled. The panel expressed concern that data from the clinical trial did not show any increase in quality of life or prolonging of life for patients—two important benchmarks for late-stage [[cancer]] treatments. The [[clinical trial]] did show that bevacizumab reduced tumor volumes and showed an increase in [[Progression Free Survival|progression free survival time]]. It was based on this data that the FDA chose to overrule the recommendation of the panel of advisers. This decision was lauded by patient advocacy groups and some oncologists. Other oncologists felt that granting approval for late-stage cancer therapies that did not prolong or increase the quality of life for patients would give license to [[pharmaceutical companies]] to ignore these important benchmarks when developing new late-stage cancer therapies.<ref name="nytimesref" />

In 2010, before the FDA announcement, The [[National Comprehensive Cancer Network]] (NCCN) updated the NCCN Clinical Practice Guidelines for Oncology (NCCN Guidelines) for Breast Cancer to affirm the recommendation regarding the use of bevacizumab in the treatment of metastatic breast cancer.{{Citation needed|date=July 2011}}

In 2011, the US Food and Drug Administration removed bevacizumab indication for metastatic breast cancer after concluding that the drug has not been shown to be safe and effective. The specific indication that was withdrawn was for the use of bevacizumab in metastatic breast cancer, with paclitaxel for the treatment of people who have not received chemotherapy for metastatic HER2-negative breast cancer.{{citation needed|date=January 2020}}

===Counterfeit===
In February 2012, Roche and its US biotech unit Genentech announced that counterfeit Avastin had been distributed in the United States.<ref>{{cite news | url=https://www.reuters.com/article/us-counterfeits-cancer-drug-avastin-foun-idUSTRE81E1TK20120215 | work=Reuters | title=Counterfeits of cancer drug Avastin found in U.S | date=15 February 2012 | url-status=live | archive-url=https://web.archive.org/web/20150924162348/http://www.reuters.com/article/2012/02/15/us-counterfeits-cancer-drug-avastin-foun-idUSTRE81E1TK20120215 | archive-date=24 September 2015 }}</ref> The investigation is ongoing, but differences in the outer packaging make identification of the bogus drugs simple for medical providers. Roche analyzed three bogus vials of Avastin and found they contained [[salt]], [[starch]], [[citrate]], [[isopropanol]], [[propanediol]], [[t-butanol]], [[benzoic acid]], di-fluorinated benzene ring, [[acetone]] and [[phthalate]] moiety, but no active ingredients of the cancer drug. According to Roche, the levels of the chemicals were not consistent; whether the chemicals were at harmful concentrations could not therefore be determined. The counterfeit Avastin has been traced back to Egypt, and it entered legitimate supply chains via Europe to the United States.<ref>{{cite news|url=http://uk.reuters.com/article/us-avastin-idUKTRE81Q29X20120227|title=Fake Avastin had salt, starch, chemicals:Roche| vauthors = Berkrot B |work=Reuters|date=27 February 2012|access-date=28 February 2012|url-status=dead|archive-url=https://web.archive.org/web/20120303111906/http://uk.reuters.com/article/2012/02/27/us-avastin-idUKTRE81Q29X20120227|archive-date=3 March 2012}}</ref><ref>{{cite web|url=http://www.fiercepharma.com/story/phony-avastin-vials-contained-chemicals-no-drugs/2012-02-28|title=Phony Avastin vials contained chemicals, but no drugs| vauthors = Staton T |publisher=FiercePharma|date=28 February 2012|access-date=28 February 2012|url-status=live|archive-url=https://web.archive.org/web/20120301191359/http://www.fiercepharma.com/story/phony-avastin-vials-contained-chemicals-no-drugs/2012-02-28|archive-date=1 March 2012}}</ref>

===Biosimilars===
{{see also|Biosimilars}}

In July 2014, two [[Pharming (genetics)|pharming]] companies, PlantForm and PharmaPraxis, announced plans to commercialize a [[biosimilar]] version of bevacizumab made using a [[tobacco]] expression system in collaboration with the [[Fraunhofer Society#Fraunhofer USA|Fraunhofer Center for Molecular Biology]].<ref>{{cite web | vauthors = Brennan Z | title=Brazilian JV to tap plant-based manufacturing system for biosimilars | website=BioPharma-Reporter | date=23 July 2014 | url=https://www.biopharma-reporter.com/Article/2014/07/23/Brazilian-JV-to-tap-plant-based-manufacturing-system-for-biosimilars | access-date=18 March 2020 | archive-url=https://web.archive.org/web/20160110103112/http://www.biopharma-reporter.com/Bio-Developments/Brazilian-JV-to-tap-plant-based-manufacturing-system-for-biosimilars |archive-date=10 January 2016 | url-status=live }}</ref>{{update inline|date=September 2020}}

In September 2017, the US FDA approved Amgen's biosimilar (generic name bevacizumab-awwb, product name Mvasi) for six cancer indications.<ref name="FDA PR 20170914">{{cite press release | title=FDA approves first biosimilar for the treatment of cancer | website=U.S. [[Food and Drug Administration]] (FDA) | date=14 September 2017 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-biosimilar-treatment-cancer | access-date=12 October 2020 | archive-date=5 November 2021 | archive-url=https://web.archive.org/web/20211105130151/https://www.fda.gov/news-events/press-announcements/fda-approves-first-biosimilar-treatment-cancer | url-status=live }} {{PD-notice}}</ref><ref>{{cite web | title=FDA approves first biosimilar for cancer treatment | website=U.S. [[Food and Drug Administration]] (FDA) | date=14 September 2017 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-first-biosimilar-cancer-treatment | access-date=12 October 2020 | archive-date=21 September 2020 | archive-url=https://web.archive.org/web/20200921111204/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-first-biosimilar-cancer-treatment | url-status=live }}</ref><ref>{{cite web | vauthors = Gever J | title=Avastin Clone OK'd — Biosimilar for bevacizumab approved for various cancers | website=MedPage Today | date=14 September 2017 | url=https://www.medpagetoday.com/hematologyoncology/othercancers/67911 | access-date=18 March 2020 | archive-url=https://web.archive.org/web/20170916225416/https://www.medpagetoday.com/HematologyOncology/OtherCancers/67911 | archive-date=16 September 2017 | url-status=live }}</ref>

In January 2018, Mvasi was approved for use in the European Union.<ref name="Mvasi EPAR">{{cite web | title=Mvasi EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/mvasi | access-date=2 April 2020 | archive-date=30 December 2019 | archive-url=https://web.archive.org/web/20191230161123/https://www.ema.europa.eu/en/medicines/human/EPAR/mvasi | url-status=live }}</ref>

In February 2019, Zirabev was approved for use in the European Union.<ref name="Zirabev EPAR">{{cite web | title=Zirabev EPAR | website=[[European Medicines Agency]] (EMA) | date=11 December 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zirabev | access-date=2 April 2020 | archive-date=30 December 2019 | archive-url=https://web.archive.org/web/20191230160954/https://www.ema.europa.eu/en/medicines/human/EPAR/zirabev | url-status=live }}</ref> Zirabev was approved for medical use in the United States in June 2019,<ref>{{cite web | title=Drug Approval Package: Zirabev | website=U.S. [[Food and Drug Administration]] (FDA) | date=14 August 2019 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761099Orig1s000TOC.cfm | access-date=29 December 2021 | archive-date=18 December 2019 | archive-url=https://web.archive.org/web/20191218044943/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761099Orig1s000TOC.cfm | url-status=live }}</ref> and in Australia in November 2019.<ref name="AU biosimilar" />

In June 2020, Mvasi was approved for medical use in Australia.<ref name="AU biosimilar" />

In August 2020, Aybintio was approved for use in the European Union.<ref name="Aybintio EPAR">{{cite web | title=Aybintio EPAR | website=[[European Medicines Agency]] (EMA) | date=26 May 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/aybintio | access-date=9 September 2020 | archive-date=29 December 2020 | archive-url=https://web.archive.org/web/20201229221338/https://www.ema.europa.eu/en/medicines/human/EPAR/aybintio | url-status=live }}</ref>

In September 2020, Equidacent was approved for use in the European Union.<ref name="Equidacent EPAR">{{cite web | title=Equidacent EPAR | website=[[European Medicines Agency]] (EMA) | date=20 July 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/equidacent | access-date=12 October 2020 | archive-date=13 October 2020 | archive-url=https://web.archive.org/web/20201013000306/https://www.ema.europa.eu/en/medicines/human/EPAR/equidacent | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

In January 2021, the [[Committee for Medicinal Products for Human Use]] (CHMP) of the [[European Medicines Agency]] (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Alymsys, intended for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer, and carcinoma of the cervix.<ref name="Alymsys EPAR" /> Alymsys was approved for medical use in the European Union in March 2021.<ref name="Alymsys EPAR">{{cite web | title=Alymsys EPAR | website=[[European Medicines Agency]] (EMA) | date=25 January 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/alymsys | access-date=19 May 2021 | archive-date=8 October 2021 | archive-url=https://web.archive.org/web/20211008120839/https://www.ema.europa.eu/en/medicines/human/EPAR/alymsys | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

In January 2021, Onbevzi was approved for medical use in the European Union.<ref name="Onbevzi EPAR">{{cite web | title=Onbevzi EPAR | website=[[European Medicines Agency]] (EMA) | date=9 November 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/onbevzi | access-date=19 May 2021 | archive-date=5 November 2021 | archive-url=https://web.archive.org/web/20211105130152/https://www.ema.europa.eu/en/medicines/human/EPAR/onbevzi | url-status=live }}</ref>

In June 2019, and June 2021, Zirabev was approved for medical use in Canada.<ref>{{cite web | title=Summary Basis of Decision (SBD) for Zirabev | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00449&lang=en | access-date=29 May 2022 | archive-date=31 May 2022 | archive-url=https://web.archive.org/web/20220531054646/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00449&lang=en | url-status=live }}</ref><ref>{{cite web | title=Summary Basis of Decision (SBD) for Zirabev | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00543&lang=en | access-date=29 May 2022 | archive-date=30 May 2022 | archive-url=https://web.archive.org/web/20220530041510/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00543&lang=en | url-status=live }}</ref>

Oyavas was approved for medical use in the European Union in March 2021.<ref name="Oyavas EPAR">{{cite web | title=Oyavas EPAR | website=European Medicines Agency | date=25 January 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/oyavas | access-date=3 March 2023 | archive-date=8 October 2021 | archive-url=https://web.archive.org/web/20211008175537/https://www.ema.europa.eu/en/medicines/human/EPAR/oyavas | url-status=live }}</ref>

Abevmy was approved for medical use in the European Union in April 2021,<ref name="Abevmy EPAR">{{cite web | title=Abevmy EPAR | website=[[European Medicines Agency]] (EMA) | date=24 February 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/abevmy | access-date=27 August 2021 | archive-date=28 August 2021 | archive-url=https://web.archive.org/web/20210828061650/https://www.ema.europa.eu/en/medicines/human/EPAR/abevmy | url-status=live }}</ref> and in Australia in September 2021.<ref name="Abevmy APM summary" /><ref name="AU biosimilar">{{cite web | title=Which biosimilar medicines are available in Australia? | url=https://www1.health.gov.au/internet/main/publishing.nsf/Content/biosimilar-which-medicines-are-available-in-australia | access-date=29 December 2021 | archive-date=30 December 2021 | archive-url=https://web.archive.org/web/20211230035404/https://www1.health.gov.au/internet/main/publishing.nsf/Content/biosimilar-which-medicines-are-available-in-australia | url-status=live }}</ref>

In September 2021, Bambevi was approved for medical use in Canada.<ref name="Bambevi SBD">{{cite web | title=Summary Basis of Decision (SBD) for Bambevi | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00568&lang=en | access-date=29 May 2022 | archive-date=29 May 2022 | archive-url=https://web.archive.org/web/20220529194052/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00568&lang=en | url-status=live }}</ref>

Bevacip and Bevaciptin were approved for medical use in Australia in November 2021.<ref name="AU biosimilar" /><ref>{{cite web | title=Bevacip/Bevaciptin | website=Therapeutic Goods Administration (TGA) | date=16 November 2021 | url=https://www.tga.gov.au/apm-summary/bevacipbevaciptin | access-date=29 December 2021 | archive-date=30 December 2021 | archive-url=https://web.archive.org/web/20211230040027/https://www.tga.gov.au/apm-summary/bevacipbevaciptin | url-status=live }}</ref>

In November 2021, Abevmy and Aybintio were approved for medical use in Canada.<ref name="Abevmy SBD">{{cite web | title=Summary Basis of Decision (SBD) for Abevmy | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00587&lang=en | access-date=29 May 2022 | archive-date=29 May 2022 | archive-url=https://web.archive.org/web/20220529191500/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00587&lang=en | url-status=live }}</ref><ref name="Aybintio SBD">{{cite web | title=Summary Basis of Decision (SBD) for Aybintio | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00574&lang=en | access-date=29 May 2022 | archive-date=29 May 2022 | archive-url=https://web.archive.org/web/20220529193156/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00574&lang=en | url-status=live }}</ref>

In April 2022, bevacizumab-maly (Alymsys) was approved for medical use in the United States.<ref name="Alymsys FDA label" />

In August 2022, Vegzelma was approved for medical use in the European Union.<ref name="Vegzelma EPAR">{{cite web | title=Vegzelma EPAR | website=[[European Medicines Agency]] (EMA) | date=20 June 2022 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/vegzelma | access-date=3 March 2023 | archive-date=28 January 2023 | archive-url=https://web.archive.org/web/20230128020239/https://www.ema.europa.eu/en/medicines/human/EPAR/vegzelma | url-status=live }}</ref><ref>{{cite web | title=Vegzelma Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1667.htm | access-date=3 March 2023 | archive-date=4 March 2023 | archive-url=https://web.archive.org/web/20230304053523/https://ec.europa.eu/health/documents/community-register/html/h1667.htm | url-status=live }}</ref>

In September 2022, bevacizumab-adcd (Vegzelma) was approved for medical use in the United States.<ref name="Vegzelma FDA label">{{cite web | title=Vegzelma- bevacizumab-adcd injection, solution | website=DailyMed | date=23 November 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4cdcccda-7b9a-49d0-ac50-f4605a3c0ebe | access-date=11 February 2023 | archive-date=11 February 2023 | archive-url=https://web.archive.org/web/20230211065131/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4cdcccda-7b9a-49d0-ac50-f4605a3c0ebe | url-status=live }}</ref>

In June 2023, Enzene Biosciences launched its bevacizumab biosimilar in India.<ref>[https://chemindigest.com/enzene-biosciences-launches-bevacizumab Enzene Biosciences Launches Bevacizumab] {{Webarchive|url=https://web.archive.org/web/20240310055617/https://chemindigest.com/enzene-biosciences-launches-bevacizumab/ |date=10 March 2024 }} 29 June 2023</ref>

Bevacizumab-tnjn (Avzivi) was approved for medical use in the United States in December 2023.<ref>{{cite web | title = Avzivi (bevacizumab-tnjn) injection, for intravenous use | work = Bio-Thera Solutions, Ltd. | publisher = U.S. Food and Drug Administration | date = 2020 | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761198s000lbl.pdf | access-date = 10 December 2023 | archive-date = 10 December 2023 | archive-url = https://web.archive.org/web/20231210100524/https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761198s000lbl.pdf | url-status = live }}</ref><ref>{{cite web | title=Biosimilar Drug Information | website=U.S. Food and Drug Administration | date=8 December 2023 | url=https://www.fda.gov/drugs/biosimilars/biosimilar-product-information | access-date=10 December 2023 | archive-date=28 August 2021 | archive-url=https://web.archive.org/web/20210828185647/https://www.fda.gov/drugs/biosimilars/biosimilar-product-information | url-status=live }}</ref>

In May 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Avzivi, intended for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer and carcinoma of the cervix.<ref name="Avzivi EPAR" /><ref>{{cite press release | title=Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 27-30 May 2024 | website=European Medicines Agency | date=31 May 2024 | url=https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-27-30-may-2024 | access-date=13 June 2024}}</ref> The applicant for this medicinal product is FGK Representative Service GmbH.<ref name="Avzivi EPAR">{{cite web | title=Avzivi EPAR | website=European Medicines Agency | date=30 May 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/avzivi | access-date=31 May 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Avzivi was approved for medical use in the European Union in July 2024.<ref name="Avzivi EPAR" /><ref name="Avzivi PI">{{cite web | title=Avzivi Public Health | website=Union Register of medicinal products | date=30 July 2024 | url=https://ec.europa.eu/health/documents/community-register/html/h1834.htm | access-date=5 August 2024}}</ref>

==Research==
A study released in April 2009, found that bevacizumab is not effective at preventing recurrences of non-metastatic colon cancer following surgery.<ref>{{cite news | vauthors = Reed K |title=Roche drug Avastin fails cancer study, shares fall |newspaper=Reuters |date=22 April 2009 |url=https://www.reuters.com/article/euRegulatoryNews/idUSLM27429520090422 |access-date=22 April 2009 |url-status=live |archive-url=https://web.archive.org/web/20090812201839/http://www.reuters.com/article/euRegulatoryNews/idUSLM27429520090422 |archive-date=12 August 2009 }}</ref>

Bevacizumab has been tested in [[ovarian cancer]] where it has shown improvement in progression-free survival but not in overall survival.<ref name="pmid27852039">{{cite journal | vauthors = Rossi L, Verrico M, Zaccarelli E, Papa A, Colonna M, Strudel M, Vici P, Bianco V, Tomao F | title = Bevacizumab in ovarian cancer: A critical review of phase III studies | journal = Oncotarget | volume = 8 | issue = 7 | pages = 12389–12405 | date = February 2017 | pmid = 27852039 | pmc = 5355353 | doi = 10.18632/oncotarget.13310 }}</ref> and [[glioblastoma multiforme]] where it failed to improve overall survival.<ref name="pmid28527008">{{cite journal | vauthors = Diaz RJ, Ali S, Qadir MG, De La Fuente MI, Ivan ME, Komotar RJ | title = The role of bevacizumab in the treatment of glioblastoma | journal = Journal of Neuro-Oncology | volume = 133 | issue = 3 | pages = 455–467 | date = July 2017 | pmid = 28527008 | doi = 10.1007/s11060-017-2477-x | s2cid = 4964000 }}</ref><ref name="pmid30119081">{{cite journal | vauthors = Kim MM, Umemura Y, Leung D | title = Bevacizumab and Glioblastoma: Past, Present, and Future Directions | journal = Cancer Journal | location = Sudbury, Mass. | volume = 24 | issue = 4 | pages = 180–186 | date = 2018 | pmid = 30119081 | doi = 10.1097/PPO.0000000000000326 | s2cid = 52033623 }}</ref>

Bevacizumab has been investigated as a possible treatment of [[pancreatic cancer]], as an addition to chemotherapy, but studies have shown no improvement in survival.<ref>{{cite journal | vauthors = Rocha-Lima CM | title = New directions in the management of advanced pancreatic cancer: a review | journal = Anti-Cancer Drugs | volume = 19 | issue = 5 | pages = 435–46 | date = June 2008 | pmid = 18418211 | doi = 10.1097/CAD.0b013e3282fc9d11 | s2cid = 25507290 }}</ref><ref>{{cite book|pages=123–9 |doi=10.1007/978-3-540-71279-4_14 |pmid=18084954 |chapter=Antiangiogenic Strategies in Pancreatic Cancer |title=Pancreatic Cancer |series=Recent Results in Cancer Research |year=2008 | vauthors = Riess H |isbn=978-3-540-71266-4 |volume=177}}</ref> It may also cause higher rates of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations.{{medcn|date=March 2020}}

The drug has also undergone trials as an addition to established chemotherapy protocols and surgery in the treatment of pediatric osteosarcoma,<ref name="pmid28631382">{{cite journal | vauthors = Navid F, Santana VM, Neel M, McCarville MB, Shulkin BL, Wu J, Billups CA, Mao S, Daryani VM, Stewart CF, Kunkel M, Smith W, Ward D, Pappo AS, Bahrami A, Loeb DM, Reikes Willert J, Rao BN, Daw NC | title = A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy | journal = International Journal of Cancer | volume = 141 | issue = 7 | pages = 1469–1477 | date = October 2017 | pmid = 28631382 | pmc = 5812455 | doi = 10.1002/ijc.30841 }}</ref> and other sarcomas, such as leiomyosarcoma.<ref name="pmid29759566">{{cite journal | vauthors = Bogani G, Ditto A, Martinelli F, Signorelli M, Chiappa V, Fonatella C, Sanfilippo R, Leone Roberti Maggiore U, Ferrero S, Lorusso D, Raspagliesi F | title = Role of bevacizumab in uterine leiomyosarcoma | journal = Critical Reviews in Oncology/Hematology | volume = 126 | pages = 45–51 | date = June 2018 | pmid = 29759566 | doi = 10.1016/j.critrevonc.2018.03.019 | s2cid = 46890425 }}</ref>

Bevacizumab has been studied as a treatment for [[vestibular schwannoma|cancers that grow from the nerve connecting the ear and the brain]].<ref>{{cite journal | vauthors = Plotkin SR, Merker VL, Halpin C, Jennings D, McKenna MJ, Harris GJ, Barker FG | title = Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients | journal = Otology & Neurotology | volume = 33 | issue = 6 | pages = 1046–52 | date = August 2012 | pmid = 22805104 | doi = 10.1097/MAO.0b013e31825e73f5 | s2cid = 205755932 | url = https://dash.harvard.edu/bitstream/1/33788498/2/Plotkin%20et%20al%202012%20-%20bevacizumab%20for%20progressive%20vestibular%20schwannoma%20in%20neurofibromatosis%20type%202%20-%20a%20retrospective%20review%20of%2031%20patients.pdf | access-date = 2 August 2019 | archive-date = 10 March 2024 | archive-url = https://web.archive.org/web/20240310055427/https://dash.harvard.edu/bitstream/handle/1/33788498/Plotkin%20et%20al%202012%20-%20bevacizumab%20for%20progressive%20vestibular%20schwannoma%20in%20neurofibromatosis%20type%202%20-%20a%20retrospective%20review%20of%2031%20patients.pdf?sequence=2 | url-status = live }}<!-- http://nrs.harvard.edu/urn-3:HUL.InstRepos:33788498 --></ref>

== References ==
{{Reflist}}

== Further reading ==
* {{cite news | vauthors = Berenson A |title=A Cancer Drug Shows Promise, at a Price That Many Can't Pay |newspaper=[[The New York Times]] |date=15 February 2006 |url=https://www.nytimes.com/2006/02/15/business/15drug.html |ref=none}}
* {{cite journal | vauthors = Sachdev JC, Jahanzeb M | title = Evolution of bevacizumab-based therapy in the management of breast cancer | journal = Clinical Breast Cancer | volume = 8 | issue = 5 | pages = 402–10 | date = October 2008 | pmid = 18952553 | doi = 10.3816/CBC.2008.n.048 |ref=none }}

== External links ==
* {{cite web | title=Bevacizumab | website=NCI Drug Dictionary | url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/bevacizumab }}

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