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{{Short description|Chemical compound}}
{{Infobox drug
{{Infobox drug
⚫
| drug_name =
| INN =
| type = <!-- empty -->
| image = Cabozantinib.svg
| image = Cabozantinib.svg
| alt =
| alt =
| caption =
| caption =


<!-- Clinical data -->
<!-- Clinical data -->
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| Drugs.com = {{drugs.com|monograph|cabozantinib-s-malate}}
| Drugs.com = {{drugs.com|monograph|cabozantinib-s-malate}}
| MedlinePlus = a613015
| MedlinePlus = a613015
| licence_EU = yes
| DailyMedID = Cabozantinib
| DailyMedID = Cabozantinib
| licence_US = Cabozantinib
| pregnancy_AU = D
| pregnancy_AU = D
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Cabozantinib Use During Pregnancy | website=Drugs.com | date=30 March 2020 | url=https://www.drugs.com/pregnancy/cabozantinib.html | access-date=23 September 2020}}</ref>
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Cabozantinib Use During Pregnancy | website=Drugs.com | date=30 March 2020 | url=https://www.drugs.com/pregnancy/cabozantinib.html | access-date=23 September 2020}}</ref>
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| ATC_prefix = L01
| ATC_prefix = L01
| ATC_suffix = EX07
| ATC_suffix = EX07
| ATC_supplemental =
| ATC_supplemental =


<!-- Legal status -->
<!-- Legal status -->
| legal_AU = S4
| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Cabometyx (Ipsen Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=13 January 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/cabometyx-ipsen-pty-ltd-3 | access-date=9 April 2023}}</ref><ref>{{cite web | title=Cabometyx cabozantinib (as (S)-malate) 20 mg film-coated tablet bottle (283800) | website=Therapeutic Goods Administration (TGA) | date=27 May 2022 | url=https://www.tga.gov.au/resources/artg/283800 | access-date=9 April 2023}}</ref><ref>{{cite web | title=AusPAR: Cabozantinib | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/auspar/auspar-cabozantinib | access-date=9 April 2023}}</ref>
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Summary Basis of Decision (SBD) for Cabometyx | website=[[Health Canada]] | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00419&lang=en | access-date=29 May 2022}}</ref><ref>{{cite web | title=Drug and medical device highlights 2018: Helping you maintain and improve your health | website=[[Health Canada]] | date=14 October 2020 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/drug-medical-device-highlights-2018.html | access-date=17 April 2024}}</ref>
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_DE_comment =
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| index2_label = as salt
| index2_label = as salt
| CAS_number = 849217-68-1
| CAS_number = 849217-68-1
| CAS_number2 = 1140909-48-3
| CAS_supplemental =
| CAS_supplemental =
| PubChem = 25102847
| PubChem = 25102847
| IUPHAR_ligand =
| IUPHAR_ligand =
| DrugBank = DB08875
| DrugBank = DB08875
| DrugBank2 = DBSALT001762
| ChemSpiderID = 25948202
| ChemSpiderID = 25948202
| ChemSpiderID2 = 25948203
| UNII = 1C39JW444G
| UNII = 1C39JW444G
⚫
| UNII2 = DR7ST46X58
| KEGG = D10062
| KEGG = D10062
| KEGG2 = D10095
| KEGG2 = D10095
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 72317
| ChEBI = 72317
| ChEBI2 = 72319
| ChEMBL = 2105717
| ChEMBL = 2105717
| ChEMBL2 = 2103868
| NIAID_ChemDB =
| NIAID_ChemDB =
| PDB_ligand =
| PDB_ligand =
| synonyms = XL184, BMS907351
| synonyms = XL184, BMS907351, cabozantinib s-malate


<!-- Chemical and physical data -->
<!-- Chemical and physical data -->
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}}
}}


'''Cabozantinib''', sold under the brand names '''Cometriq''' and '''Cabometyx''' among others, is a medication used to treat [[medullary thyroid cancer]], [[renal cell carcinoma]], and [[hepatocellular carcinoma]]. It is a [[small molecule]] [[Tyrosine-kinase inhibitor|inhibitor of the tyrosine kinases]] [[c-Met]] and [[VEGFR2]], and also inhibits [[AXL receptor tyrosine kinase|AXL]] and RET. It was discovered and developed by [[Exelixis]] Inc.
'''Cabozantinib''', sold under the brand names '''Cometriq''' and '''Cabometyx''' among others, is an [[anti-cancer medication]] used to treat [[medullary thyroid cancer]], [[renal cell carcinoma]], and [[hepatocellular carcinoma]].<ref name="Cabometyx tablet FDA label" /><ref name="Cometriq capsule FDA label" /> It is a [[small-molecule]] [[tyrosine-kinase inhibitor]] (TKI) of [[c-Met]] (HGFR) and [[VEGFR2]], and also inhibits [[AXL receptor tyrosine kinase|AXL]], [[RET proto-oncogene|RET]], and [[Fms-like tyrosine kinase 3|FLT3]].<ref name=UKlabelCapsule/><ref name=UKlabelTablet/> It was discovered and developed by [[Exelixis]] Inc.


In November 2012, cabozantinib in its capsule formulation was approved by the U.S. [[Food and Drug Administration]] (FDA) under the name Cometriq for treating patients with [[medullary thyroid cancer]].<ref name=FDA2012/><ref name="Cometriq FDA approval" /> The capsule form was approved in the European Union for the same purpose in 2014.<ref name="Cometriq EPAR"/>
In November 2012, cabozantinib in its capsule formulation was approved by the US [[Food and Drug Administration]] (FDA) under the name Cometriq for treating people with [[medullary thyroid cancer]].<ref name=FDA2012/><ref name="Cometriq FDA approval" /> The capsule form was approved in the European Union for the same purpose in 2014.<ref name="Cometriq EPAR"/> In April 2016, the FDA granted approval for marketing the tablet formulation (Cabometyx) as a second line treatment for [[kidney cancer]]<ref name=FDA2016-04/><ref name="Cabometyx FDA approval" /> and the same was approved in the European Union in September of that year.<ref name="Cabometyx EPAR"/> The brands Cometriq and Cabometyx have different formulations and are not interchangeable.<ref name="FDA Cabometyx 20171219" />

In April 2016, the FDA granted approval for marketing the tablet formulation (Cabometyx) as a second line treatment for [[kidney cancer]]<ref name=FDA2016-04/><ref name="Cabometyx FDA approval" /> and the same was approved in the European Union in September of that year.<ref name="Cabometyx EPAR"/>

The brands Cometriq and Cabometyx have different formulations and are not interchangeable.<ref name="FDA Cabometyx 20171219" />


==Medical uses==
==Medical uses==
Cabozantinib is used in two forms. A capsule form (Cometriq) is used since 2012, to treat [[medullary thyroid cancer]]<ref name="Cometriq capsule FDA label" /><ref name=UKlabelCapsule>{{cite web|title=Cabozantinib capsule (Cometriq) UK Summary of Product Characteristics (SPC) - (eMC)|url=https://www.medicines.org.uk/emc/medicine/32559|publisher=UK Electronic Medicines Compendium|date=November 2016}}</ref> and a tablet form (Cabometyx) is used since 2016, as a second line treatment for [[renal cell carcinoma]].<ref name="Cabometyx tablet FDA label" /><ref name=UKlabelTablet>{{cite web|title=Cabozantinib tablet (Cabometyx) UK Summary of Product Characteristics|url=https://www.medicines.org.uk/emc/medicine/32431|publisher=UK Electronic Medicines Compendium|date=September 2016}}</ref>
Cabozantinib is used in two forms. A capsule form (Cometriq) is used to treat [[medullary thyroid cancer]]<ref name="Cometriq capsule FDA label" /><ref name=UKlabelCapsule>{{cite web | title=Cometriq 20 & 80 mg hard capsules - Summary of Product Characteristics (SmPC) | website=(emc) | date=6 October 2022 | url=https://www.medicines.org.uk/emc/medicine/32559 | access-date=9 April 2023}}</ref> and a tablet form (Cabometyx) is used to treat [[renal cell carcinoma]], hepatocellular carcinoma, and differentiated thyroid carcinoma.<ref name="Cabometyx tablet FDA label" /><ref name=UKlabelTablet>{{cite web | title=Cabometyx 20mg, 40mg, 60mg - Summary of Product Characteristics (SmPC) | website=(emc) | date=7 October 2022 | url=https://www.medicines.org.uk/emc/medicine/32431 | access-date=9 April 2023}}</ref><ref>{{cite web | title=FDA approves cabozantinib for differentiated thyroid cancer | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=22 September 2021 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cabozantinib-differentiated-thyroid-cancer | access-date=22 September 2021}} {{PD-notice}}</ref>

In the United States, cabozantinib (Cabometyx) is also indicated for the treatment of people aged twelve years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are ineligible or refractory to radioactive iodine.<ref>{{cite web | title=FDA approves cabozantinib for differentiated thyroid cancer | website=U.S. Food and Drug Administration | date=22 September 2021 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cabozantinib-differentiated-thyroid-cancer | access-date=22 September 2021}} {{PD-notice}}</ref>


==Contraindications==
==Contraindications==
Cabozantinib has not been tested in pregnant women; it causes harm to fetuses in rodents. Pregnant women should not take this drug, and women should not become pregnant while taking it. It is not known if cabozantinib is excreted in breast milk.<ref name=UKlabelCapsule/><ref name=UKlabelTablet/>
Cabozantinib has not been tested in pregnant women; it causes harm to fetuses in rodents. Pregnant women should not take this drug, and women should not become pregnant while taking it. It is not known if cabozantinib is excreted in breast milk.<ref name=UKlabelCapsule/><ref name=UKlabelTablet/>

The drug should be used with caution in people with a history of heart rhythm problems, including long QT interval.<ref name=UKlabelTablet/>


==Adverse effects==
==Adverse effects==
In the US, the capsule formulation (Cometriq) carries a [[black box warning]] of the risk of [[gastrointestinal perforation|holes forming in the stomach or intestines]] as well as formation of [[fistulas]] (tunnels between the GI tract and the skin).<ref name="Cometriq capsule FDA label"/> The black box also warns against the risk of uncontrolled bleeding.<ref name="Cometriq capsule FDA label"/> The tablet formulation (Cabometyx) warns of these effects as well.<ref name="Cabometyx tablet FDA label"/><ref name=UKlabelTablet/>
In the US, the capsule formulation (Cometriq) carries a [[black box warning]] of the risk of [[gastrointestinal perforation|holes forming in the stomach or intestines]] as well as formation of [[fistulas]] (tunnels between the GI tract and the skin).<ref name="Cometriq capsule FDA label"/> The black box also warns against the risk of uncontrolled bleeding.<ref name="Cometriq capsule FDA label"/> The tablet formulation (Cabometyx) warns of these effects as well.<ref name="Cabometyx tablet FDA label"/><ref name=UKlabelTablet/>


The labels also warn of the risk of clots forming and causing heart attacks or strokes, high blood pressure including [[hypertensive crisis]], osteonecrosis of the jaw, severe diarrhea, [[Chemotherapy-induced acral erythema|skin sloughing off the palms and soles]], [[Posterior reversible encephalopathy syndrome|a syndrome with headaches, confusion, loss of vision, and seizures]], and protein appearing in urine.<ref name="Cometriq capsule FDA label"/><ref name="Cabometyx tablet FDA label"/><ref name=UKlabelCapsule/><ref name=UKlabelTablet/>
The labels also warn of the risk of clots forming and causing heart attacks or strokes, high blood pressure including [[hypertensive crisis]], osteonecrosis of the jaw, severe diarrhea, [[Chemotherapy-induced acral erythema|skin sloughing off the palms and soles]], [[Posterior reversible encephalopathy syndrome|a syndrome with headaches, confusion, loss of vision, and seizures]], and protein appearing in urine.<ref name="Cometriq capsule FDA label"/><ref name="Cabometyx tablet FDA label"/><ref name=UKlabelCapsule/><ref name=UKlabelTablet/>
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== Interactions ==
== Interactions ==

Grapefruit and grapefruit juice should be avoided as they may increase the concentration of the drug in the blood.<ref name=UKlabelTablet/>

Cabozantinib is a substrate of [[CYP3A4]] and [[multidrug resistance-associated protein 2]]; drugs that inhibit these enzymes will increase the [[Biological half-life|half-life]] of cabozantinib and potentially increase its adverse effects; drugs that activate them may cause cabozantinib to be less effective.<ref name=UKlabelTablet/>
Cabozantinib is a substrate of [[CYP3A4]] and [[multidrug resistance-associated protein 2]]; drugs that inhibit these enzymes will increase the [[Biological half-life|half-life]] of cabozantinib and potentially increase its adverse effects; drugs that activate them may cause cabozantinib to be less effective.<ref name=UKlabelTablet/>

It inhibits [[P-glycoprotein]], so will change the availability of other drugs that depend on this transporter.<ref name=UKlabelTablet/>


==Pharmacology==
==Pharmacology==
It inhibits the following [[receptor tyrosine kinase]]s: MET (hepatocyte growth factor receptor protein) and VEGFR, RET, GAS6 receptor (AXL), KIT), and Fms-like tyrosine kinase-3 (FLT3).<ref name=UKlabelTablet/> <ref>{{cite journal | vauthors = Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH | display-authors = 6 | title = Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth | journal = Molecular Cancer Therapeutics | volume = 10 | issue = 12 | pages = 2298–2308 | date = December 2011 | pmid = 21926191 | doi = 10.1158/1535-7163.MCT-11-0264 | s2cid = 16709393 }}</ref>
Cabozantinib inhibits the following [[receptor tyrosine kinase]]s (RTKs): [[c-Met]] (HGFR), [[VEGFR2]], [[AXL receptor tyrosine kinase|AXL]], [[RET proto-oncogene|RET]], and [[Fms-like tyrosine kinase 3|FLT3]].<ref name=UKlabelTablet/><ref>{{cite journal | vauthors = Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH | display-authors = 6 | title = Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth | journal = Molecular Cancer Therapeutics | volume = 10 | issue = 12 | pages = 2298–2308 | date = December 2011 | pmid = 21926191 | doi = 10.1158/1535-7163.MCT-11-0264 | s2cid = 16709393 | url = https://figshare.com/articles/journal_contribution/22496638 | doi-access = free }}</ref>


==History==
==History==
Cabozantinib was granted [[orphan drug]] status by the U.S. [[Food and Drug Administration]] (FDA) in November 2010,<ref>{{cite web | title=Cabozantinib Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=29 November 2010 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=297109 | access-date=11 November 2020}}</ref> and in February 2017.<ref>{{cite web | title=Search Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=2 March 2017 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=552916 | access-date=11 November 2020}}</ref>
Cabozantinib was granted [[orphan drug]] status by the US [[Food and Drug Administration]] (FDA) in November 2010,<ref>{{cite web | title=Cabozantinib Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=29 November 2010 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=297109 | access-date=11 November 2020}}</ref> and in February 2017.<ref>{{cite web | title=Search Orphan Drug Designations and Approvals | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=2 March 2017 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=552916 | access-date=11 November 2020}}</ref>


Exelixis filed a [[new drug application]] with the FDA in the first half of 2012,<ref>{{cite web|url=http://www.curetoday.com/index.cfm/fuseaction/news.showNewsArticle/id/13/news_id/3299|title=Thyroid cancer drug cabozantinib prolongs PFS|access-date=24 October 2011|archive-url=https://web.archive.org/web/20120402000445/http://www.curetoday.com/index.cfm/fuseaction/news.showNewsArticle/id/13/news_id/3299|archive-date=2012-04-02|url-status=dead}}</ref> and on November 29, 2012 cabozantinib in its capsule formulation was granted marketing approval by the U.S. FDA under the name Cometriq for treating patients with [[medullary thyroid cancer]].<ref name=FDA2012>{{cite press release |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm330143.htm |title=FDA approves Cometriq to treat rare type of thyroid cancer |date= 29 November 2012|publisher=U.S. [[Food and Drug Administration]] (FDA)|archive-url=https://web.archive.org/web/20140707053649/https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm330213.htm|archive-date=July 7, 2014|url-status=dead}}</ref><ref name="Cometriq FDA approval">{{cite web | title=Drug Approval Package: Cometriq (cabozantinib) Capsules NDA #203756 | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203756Orig1s000TOC.cfm | access-date=23 September 2020 | lay-url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203756Orig1s000SumR.pdf }}</ref> The capsule form was approved in the European Union for the same purpose in 2014.<ref name="Cometriq EPAR">{{cite web | title=Cometriq EPAR | website=[[European Medicines Agency]] (EMA) | url=https://www.ema.europa.eu/en/medicines/human/EPAR/cometriq | access-date=23 September 2020}}</ref>
Exelixis filed a [[new drug application]] with the FDA in 2012,<ref>{{cite web|url=http://www.curetoday.com/index.cfm/fuseaction/news.showNewsArticle/id/13/news_id/3299|title=Thyroid cancer drug cabozantinib prolongs PFS|access-date=24 October 2011|archive-url=https://web.archive.org/web/20120402000445/http://www.curetoday.com/index.cfm/fuseaction/news.showNewsArticle/id/13/news_id/3299|archive-date=2012-04-02|url-status=dead}}</ref> and in November 2012, cabozantinib in its capsule formulation was granted marketing approval by the FDA under the name Cometriq for treating people with [[medullary thyroid cancer]].<ref name=FDA2012>{{cite press release |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm330143.htm |title=FDA approves Cometriq to treat rare type of thyroid cancer |date= 29 November 2012|publisher=U.S. [[Food and Drug Administration]] (FDA)|archive-url=https://web.archive.org/web/20140707053649/https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm330213.htm|archive-date=July 7, 2014|url-status=dead}}</ref><ref name="Cometriq FDA approval">{{cite web | title=Drug Approval Package: Cometriq (cabozantinib) Capsules NDA #203756 | publisher=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203756Orig1s000TOC.cfm | access-date=23 September 2020 }}</ref> The capsule form was approved in the European Union for the same purpose in 2014.<ref name="Cometriq EPAR">{{cite web | title=Cometriq EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/cometriq | access-date=23 September 2020}}</ref>


In March 2016 Exelixis licensed to [[Ipsen]] worldwide rights (outside the US, Canada, and Japan) to market cabozantinib.<ref>{{cite news| vauthors = Garde D |title=Ipsen bets up to $855M on Exelixis' once-failed cancer drug|url=http://www.fiercebiotech.com/partnering/ipsen-bets-up-to-855m-on-exelixis-once-failed-cancer-drug|work=FierceBiotech|date=March 1, 2016}}</ref>
In March 2016, Exelixis licensed to [[Ipsen]] worldwide rights (outside the US, Canada, and Japan) to market cabozantinib.<ref>{{cite news| vauthors = Garde D |title=Ipsen bets up to $855M on Exelixis' once-failed cancer drug|url=http://www.fiercebiotech.com/partnering/ipsen-bets-up-to-855m-on-exelixis-once-failed-cancer-drug|work=FierceBiotech|date=March 1, 2016}}</ref>


⚫
In April 2016, the FDA granted approval for marketing the tablet formulation as a second line treatment for [[kidney cancer]]<ref name=FDA2016-04>{{cite web | title=Cabozantinib (Cabometyx) | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=25 April 2016 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/cabozantinib-cabometyx | access-date=23 September 2020}}</ref><ref name="Cabometyx FDA approval">{{cite web | title=Cabometyx (cabozantinib) Tablets | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=12 January 2018 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000TOC.cfm | access-date=23 September 2020}}</ref> and the same was approved in the European Union in September of that year.<ref name="Cabometyx EPAR">{{cite web | title=Cabometyx EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/cabometyx | access-date=23 September 2020}}</ref>
⚫
Exelixis' Phase III trial results of testing the drug in renal cancer published in the NEJM in 2015.<ref>{{cite journal | vauthors = Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Géczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ | display-authors = 6 | title = Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma | journal = The New England Journal of Medicine | volume = 373 | issue = 19 | pages = 1814–1823 | date = November 2015 | pmid = 26406150 | pmc = 5024539 | doi = 10.1056/nejmoa1510016 }}</ref>
⚫
In April 2016 the FDA granted approval for marketing the tablet formulation as a second line treatment for [[kidney cancer]]<ref name=FDA2016-04>{{cite web | title=Cabozantinib (Cabometyx) | website=U.S. [[Food and Drug Administration]] (FDA) | date=25 April 2016 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/cabozantinib-cabometyx | access-date=23 September 2020}}</ref><ref name="Cabometyx FDA approval">{{cite web | title=Cabometyx (cabozantinib) Tablets | website=U.S. [[Food and Drug Administration]] (FDA) | date=12 January 2018 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208692Orig1s000TOC.cfm | access-date=23 September 2020}}</ref> and the same was approved in the European Union in September of that year.<ref name="Cabometyx EPAR">{{cite web | title=Cabometyx EPAR | website=[[European Medicines Agency]] (EMA) | url=https://www.ema.europa.eu/en/medicines/human/EPAR/cabometyx | access-date=23 September 2020}}</ref>


In December 2017, the FDA granted approval to cabozantinib (Cabometyx, Exelixis, Inc.) for treatment of people with advanced renal cell carcinoma (RCC).<ref name="FDA Cabometyx 20171219">{{cite web | title=FDA grants regular approval to Cabometyx for first-line treatment of a | website=U.S. [[Food and Drug Administration]] (FDA) | date=19 December 2017 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-cabometyx-first-line-treatment-advanced-renal-cell-carcinoma | access-date=23 September 2020}} {{PD-notice}}</ref> The approval was based on data from CABOSUN (NCT01835158), a randomized, open-label phase II multicenter study in 157 participants with intermediate and poor-risk previously untreated RCC.<ref name="FDA Cabometyx 20171219" />
In December 2017, the FDA granted approval to cabozantinib (Cabometyx, Exelixis, Inc.) for the treatment of people with advanced renal cell carcinoma (RCC).<ref name="FDA Cabometyx 20171219">{{cite web | title=FDA grants regular approval to Cabometyx for first-line treatment of a | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=19 December 2017 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-cabometyx-first-line-treatment-advanced-renal-cell-carcinoma | access-date=23 September 2020}} {{PD-notice}}</ref> The approval was based on data from CABOSUN (NCT01835158), a randomized, open-label phase II multicenter study in 157 participants with intermediate and poor-risk previously untreated RCC.<ref name="FDA Cabometyx 20171219" />


In January 2019, the FDA approved cabozantinib (Cabometyx, Exelixis, Inc.) for people with hepatocellular carcinoma (HCC) who have been previously treated with [[sorafenib]].<ref name="FDA Cabometyx 20190114">{{cite web | title=FDA approves cabozantinib for hepatocellular carcinoma | website=U.S. [[Food and Drug Administration]] (FDA) | date=14 January 2019 | url=https://www.fda.gov/drugs/fda-approves-cabozantinib-hepatocellular-carcinoma | access-date=23 September 2020}} {{PD-notice}}</ref> The approval was based on CELESTIAL (NCT01908426), a randomized (2:1), double-blind, placebo-controlled, multicenter trial in participants with HCC who had previously received sorafenib and had [[Cirrhosis|Child Pugh Class A liver impairment]].
In January 2019, the FDA approved cabozantinib (Cabometyx, Exelixis, Inc.) for people with hepatocellular carcinoma who have been previously treated with [[sorafenib]].<ref name="FDA Cabometyx 20190114">{{cite web | title=FDA approves cabozantinib for hepatocellular carcinoma | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=14 January 2019 | url=https://www.fda.gov/drugs/fda-approves-cabozantinib-hepatocellular-carcinoma | access-date=23 September 2020}} {{PD-notice}}</ref> The approval was based on CELESTIAL (NCT01908426), a randomized (2:1), double-blind, placebo-controlled, multicenter trial in participants with hepatocellular carcinoma who had previously received sorafenib and had [[Cirrhosis|Child Pugh Class A liver impairment]].


== Research ==
== Research ==
Cabozantinib is being researched<ref>{{Cite web|title=Search of: cabozantinib {{!}} Recruiting, Active, not recruiting, Enrolling by invitation Studies - List Results - ClinicalTrials.gov|url=https://clinicaltrials.gov/ct2/results?term=cabozantinib&Search=Apply&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=&rslt=|access-date=2021-08-09|website=clinicaltrials.gov|language=en}}</ref> for efficacy as a treatment for [[renal cell carcinoma]] (RCC), [[hepatocellular carcinoma]] (HCC), [[cervical cancer]], [[colorectal cancer]] (CRC), [[Transitional cell carcinoma|urothelial cancer]], [[prostate cancer]], [[Stomach cancer|gastric]] and [[Esophageal cancer|gastroesophageal cancer]], [[bladder cancer]], [[melanoma]], [[Merkel-cell carcinoma|merkel cell carcinoma]], [[Brain tumor|brain cancers]] (including [[Glioblastoma|glioblastoma multiforme]] and [[anaplastic astrocytoma]]), [[Non-small-cell lung carcinoma|non-small cell lung cancer]] (NSCLC), [[adrenocortical carcinoma]], various [[Sarcoma|sarcomas]], [[Head and neck cancer|head and neck squamous cell carcinomas]] (HNSCC), [[breast cancer]], [[endometrial cancer]], [[Neuroendocrine tumor|neuroendocrine cancers]], and [[Neurofibromatosis type I|neurofibromatosis type 1]].<ref>{{cite journal | vauthors = Fisher MJ, Shih CS, Rhodes SD, Armstrong AE, Wolters PL, Dombi E, Zhang C, Angus SP, Johnson GL, Packer RJ, Allen JC, Ullrich NJ, Goldman S, Gutmann DH, Plotkin SR, Rosser T, Robertson KA, Widemann BC, Smith AE, Bessler WK, He Y, Park SJ, Mund JA, Jiang L, Bijangi-Vishehsaraei K, Robinson CT, Cutter GR, Korf BR, Blakeley JO, Clapp DW | display-authors = 6 | title = Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial | journal = Nature Medicine | volume = 27 | issue = 1 | pages = 165–173 | date = January 2021 | pmid = 33442015 | pmc = 8275010 | doi = 10.1038/s41591-020-01193-6 }}</ref>
Cabozantinib is being researched<ref>{{Cite web|title=Search of: cabozantinib {{!}} Recruiting, Active, not recruiting, Enrolling by invitation Studies - List Results - ClinicalTrials.gov|url=https://clinicaltrials.gov/ct2/results?term=cabozantinib&Search=Apply&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=&rslt=|access-date=2021-08-09|website=clinicaltrials.gov|language=en}}</ref> for efficacy as a treatment for [[renal cell carcinoma]] (RCC), [[hepatocellular carcinoma]] (HCC), [[cervical cancer]], [[colorectal cancer]] (CRC), [[Transitional cell carcinoma|urothelial cancer]], [[prostate cancer]], [[Stomach cancer|gastric]] and [[Esophageal cancer|gastroesophageal cancer]], [[bladder cancer]], [[melanoma]], [[Merkel-cell carcinoma|merkel cell carcinoma]], [[Brain tumor|brain cancers]] (including [[Glioblastoma|glioblastoma multiforme]] and [[anaplastic astrocytoma]]), [[Non-small-cell lung carcinoma|non-small cell lung cancer]] (NSCLC), [[adrenocortical carcinoma]], various [[sarcoma]]s, [[Head and neck cancer|head and neck squamous cell carcinomas]] (HNSCC), [[breast cancer]], [[endometrial cancer]], [[Neuroendocrine tumor|neuroendocrine cancers]], and [[Neurofibromatosis type I|neurofibromatosis type 1]].<ref>{{cite journal | vauthors = Fisher MJ, Shih CS, Rhodes SD, Armstrong AE, Wolters PL, Dombi E, Zhang C, Angus SP, Johnson GL, Packer RJ, Allen JC, Ullrich NJ, Goldman S, Gutmann DH, Plotkin SR, Rosser T, Robertson KA, Widemann BC, Smith AE, Bessler WK, He Y, Park SJ, Mund JA, Jiang L, Bijangi-Vishehsaraei K, Robinson CT, Cutter GR, Korf BR, Blakeley JO, Clapp DW | display-authors = 6 | title = Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial | journal = Nature Medicine | volume = 27 | issue = 1 | pages = 165–173 | date = January 2021 | pmid = 33442015 | pmc = 8275010 | doi = 10.1038/s41591-020-01193-6 }}</ref>


== References ==
== References ==
{{reflist}}
{{reflist}}

== Further reading ==
⚫
* {{cite journal | vauthors = Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Géczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ | display-authors = 6 | title = Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma | journal = The New England Journal of Medicine | volume = 373 | issue = 19 | pages = 1814–1823 | date = November 2015 | pmid = 26406150 | pmc = 5024539 | doi = 10.1056/nejmoa1510016 }}


== External links ==
== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/cabozantinib | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Cabozantinib }}
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/cabozantinib%20s-malate | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Cabozantinib s-malate }}
* {{cite web | title=Cabozantinib s-malate | work=NCI Drug Dictionary | publisher=National Cancer Institute | url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/cabozantinib-s-malate }}
* {{cite web | title=Cabozantinib s-malate | work=NCI Drug Dictionary | publisher=National Cancer Institute | url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/cabozantinib-s-malate }}
* {{cite web | title=Cabozantinib (liver and kidney cancer) | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a616037.html }}
* {{cite web | title=Cabozantinib-S-Malate | date=19 December 2012 | publisher=National Cancer Institute | url=https://www.cancer.gov/about-cancer/treatment/drugs/cabozantinib-s-malate}}
* {{cite web | title=Cabozantinib (liver and kidney cancer) | publisher=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a616037.html }}
* {{ClinicalTrialsGov|NCT01835158|Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer}}
* {{ClinicalTrialsGov|NCT01835158|Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer}}
* {{ClinicalTrialsGov|NCT01908426|Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib (CELESTIAL)}}
* {{ClinicalTrialsGov|NCT01908426|Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib (CELESTIAL)}}
* {{ClinicalTrialsGov|NCT03690388|A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy}}
* {{ClinicalTrialsGov|NCT03690388|A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy}}


{{Extracellular chemotherapeutic agents}}
{{Targeted cancer therapeutic agents}}
{{Growth factor receptor modulators}}
{{Growth factor receptor modulators}}
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[[Category:Antineoplastic drugs]]
[[Category:Antineoplastic drugs]]
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[[Category:Breakthrough therapy]]
[[Category:Cyclopropanes]]
[[Category:Cyclopropanes]]
[[Category:Fluoroarenes]]
[[Category:4-Fluorophenyl compounds]]
[[Category:Orphan drugs]]
[[Category:Orphan drugs]]
[[Category:Protein_kinase_inhibitors]]
[[Category:Quinolines]]
[[Category:Quinolines]]
[[Category:Tyrosine kinase inhibitors]]
[[Category:Tyrosine kinase inhibitors]]
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[[Category:Diaryl ethers]]

Latest revision as of 06:51, 18 September 2024

Cabozantinib
Clinical data
Trade namesCometriq, Cabometyx, others
Other namesXL184, BMS907351, cabozantinib s-malate
AHFS/Drugs.comMonograph
MedlinePlusa613015
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding≥99.7%
MetabolismLiver (CYP3A4-mediated)
Elimination half-life110 hours
ExcretionFeces (54%), urine (27%)
Identifiers
  • N-(4-((6,7-Dimethoxyquinolin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.221.147 Edit this at Wikidata
Chemical and physical data
FormulaC28H24FN3O5
Molar mass501.514 g·mol−1
3D model (JSmol)
  • COc1cc2nccc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3)c2cc1OC
  • InChI=1S/C28H24FN3O5/c1-35-24-15-21-22(16-25(24)36-2)30-14-11-23(21)37-20-9-7-19(8-10-20)32-27(34)28(12-13-28)26(33)31-18-5-3-17(29)4-6-18/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34)
  • Key:ONIQOQHATWINJY-UHFFFAOYSA-N

Cabozantinib, sold under the brand names Cometriq and Cabometyx among others, is an anti-cancer medication used to treat medullary thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma.[9][10] It is a small-molecule tyrosine-kinase inhibitor (TKI) of c-Met (HGFR) and VEGFR2, and also inhibits AXL, RET, and FLT3.[8][7] It was discovered and developed by Exelixis Inc.

In November 2012, cabozantinib in its capsule formulation was approved by the US Food and Drug Administration (FDA) under the name Cometriq for treating people with medullary thyroid cancer.[13][14] The capsule form was approved in the European Union for the same purpose in 2014.[11] In April 2016, the FDA granted approval for marketing the tablet formulation (Cabometyx) as a second line treatment for kidney cancer[15][16] and the same was approved in the European Union in September of that year.[12] The brands Cometriq and Cabometyx have different formulations and are not interchangeable.[17]

Medical uses

[edit]

Cabozantinib is used in two forms. A capsule form (Cometriq) is used to treat medullary thyroid cancer[10][8] and a tablet form (Cabometyx) is used to treat renal cell carcinoma, hepatocellular carcinoma, and differentiated thyroid carcinoma.[9][7][18]

Contraindications

[edit]

Cabozantinib has not been tested in pregnant women; it causes harm to fetuses in rodents. Pregnant women should not take this drug, and women should not become pregnant while taking it. It is not known if cabozantinib is excreted in breast milk.[8][7]

Adverse effects

[edit]

In the US, the capsule formulation (Cometriq) carries a black box warning of the risk of holes forming in the stomach or intestines as well as formation of fistulas (tunnels between the GI tract and the skin).[10] The black box also warns against the risk of uncontrolled bleeding.[10] The tablet formulation (Cabometyx) warns of these effects as well.[9][7]

The labels also warn of the risk of clots forming and causing heart attacks or strokes, high blood pressure including hypertensive crisis, osteonecrosis of the jaw, severe diarrhea, skin sloughing off the palms and soles, a syndrome with headaches, confusion, loss of vision, and seizures, and protein appearing in urine.[10][9][8][7]

Very common adverse effects (greater than 10% of people) include decreased appetite; low calcium, potassium, phosphate, and magnesium levels; high bilirubin levels; distorted sense of taste, headache, and dizziness; high blood pressure; distorted sense of hearing, earaches and sore throat; diarrhea, nausea, constipation, vomiting, stomach pain and upset stomach, and inflammation of the mouth and lips and a burning sensation in the mouth; skin sloughing off the palms and soles, hair color changes and hair loss, rash, dry skin, and red skin; joint pain and muscle spasms; fatigue and weakness; weight loss, elevated transaminases, higher cholesterol levels, and loss of red and white blood cells.[7]

Common adverse effects (between 1% and 10% of people) include abscesses (inside the body, on the skin, and in teeth skin), pneumonia, inflamed hair follicles, fungal infections, low thyroid levels, dehydration, loss of albumin, anxiety, depression, and confusion, peripheral neuropathy, tingling, and tremor, tinnitus, atrial fibrillation, low blood pressure, blocked veins, paleness, chills, fistulas forming in the trachea and esophagus, blood clots in the lungs, and bleeding in the respiratory tract, GI perforation, bleeding in the stomach and intestines, pancreatitis, hemorrhoids, anal fissure, anal inflammation, gallstones, hard skin growths, acne, blisters, abnormal hair growth, loss of skin color and skin flaking, chest pain, blood or protein in urine, wounds that don't heal well, and facial swelling.[7]

Interactions

[edit]

Cabozantinib is a substrate of CYP3A4 and multidrug resistance-associated protein 2; drugs that inhibit these enzymes will increase the half-life of cabozantinib and potentially increase its adverse effects; drugs that activate them may cause cabozantinib to be less effective.[7]

Pharmacology

[edit]

Cabozantinib inhibits the following receptor tyrosine kinases (RTKs): c-Met (HGFR), VEGFR2, AXL, RET, and FLT3.[7][19]

History

[edit]

Cabozantinib was granted orphan drug status by the US Food and Drug Administration (FDA) in November 2010,[20] and in February 2017.[21]

Exelixis filed a new drug application with the FDA in 2012,[22] and in November 2012, cabozantinib in its capsule formulation was granted marketing approval by the FDA under the name Cometriq for treating people with medullary thyroid cancer.[13][14] The capsule form was approved in the European Union for the same purpose in 2014.[11]

In March 2016, Exelixis licensed to Ipsen worldwide rights (outside the US, Canada, and Japan) to market cabozantinib.[23]

In April 2016, the FDA granted approval for marketing the tablet formulation as a second line treatment for kidney cancer[15][16] and the same was approved in the European Union in September of that year.[12]

In December 2017, the FDA granted approval to cabozantinib (Cabometyx, Exelixis, Inc.) for the treatment of people with advanced renal cell carcinoma (RCC).[17] The approval was based on data from CABOSUN (NCT01835158), a randomized, open-label phase II multicenter study in 157 participants with intermediate and poor-risk previously untreated RCC.[17]

In January 2019, the FDA approved cabozantinib (Cabometyx, Exelixis, Inc.) for people with hepatocellular carcinoma who have been previously treated with sorafenib.[24] The approval was based on CELESTIAL (NCT01908426), a randomized (2:1), double-blind, placebo-controlled, multicenter trial in participants with hepatocellular carcinoma who had previously received sorafenib and had Child Pugh Class A liver impairment.

Research

[edit]

Cabozantinib is being researched[25] for efficacy as a treatment for renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), cervical cancer, colorectal cancer (CRC), urothelial cancer, prostate cancer, gastric and gastroesophageal cancer, bladder cancer, melanoma, merkel cell carcinoma, brain cancers (including glioblastoma multiforme and anaplastic astrocytoma), non-small cell lung cancer (NSCLC), adrenocortical carcinoma, various sarcomas, head and neck squamous cell carcinomas (HNSCC), breast cancer, endometrial cancer, neuroendocrine cancers, and neurofibromatosis type 1.[26]

References

[edit]
  1. ^ "Cabozantinib Use During Pregnancy". Drugs.com. 30 March 2020. Retrieved 23 September 2020.
  2. ^ "Cabometyx (Ipsen Pty Ltd)". Therapeutic Goods Administration (TGA). 13 January 2023. Retrieved 9 April 2023.
  3. ^ "Cabometyx cabozantinib (as (S)-malate) 20 mg film-coated tablet bottle (283800)". Therapeutic Goods Administration (TGA). 27 May 2022. Retrieved 9 April 2023.
  4. ^ "AusPAR: Cabozantinib". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 9 April 2023.
  5. ^ "Summary Basis of Decision (SBD) for Cabometyx". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  6. ^ "Drug and medical device highlights 2018: Helping you maintain and improve your health". Health Canada. 14 October 2020. Retrieved 17 April 2024.
  7. ^ a b c d e f g h i j "Cabometyx 20mg, 40mg, 60mg - Summary of Product Characteristics (SmPC)". (emc). 7 October 2022. Retrieved 9 April 2023.
  8. ^ a b c d e "Cometriq 20 & 80 mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 6 October 2022. Retrieved 9 April 2023.
  9. ^ a b c d e "Cabometyx- cabozantinib tablet". DailyMed. 21 July 2020. Retrieved 23 September 2020.
  10. ^ a b c d e f "Cometriq- cabozantinib kit Cometriq- cabozantinib capsule". DailyMed. 11 February 2020. Retrieved 23 September 2020.
  11. ^ a b c "Cometriq EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 23 September 2020.
  12. ^ a b c "Cabometyx EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 23 September 2020.
  13. ^ a b "FDA approves Cometriq to treat rare type of thyroid cancer" (Press release). U.S. Food and Drug Administration (FDA). 29 November 2012. Archived from the original on July 7, 2014.
  14. ^ a b "Drug Approval Package: Cometriq (cabozantinib) Capsules NDA #203756". U.S. Food and Drug Administration (FDA). Retrieved 23 September 2020.
  15. ^ a b "Cabozantinib (Cabometyx)". U.S. Food and Drug Administration (FDA). 25 April 2016. Retrieved 23 September 2020.
  16. ^ a b "Cabometyx (cabozantinib) Tablets". U.S. Food and Drug Administration (FDA). 12 January 2018. Retrieved 23 September 2020.
  17. ^ a b c "FDA grants regular approval to Cabometyx for first-line treatment of a". U.S. Food and Drug Administration (FDA). 19 December 2017. Retrieved 23 September 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  18. ^ "FDA approves cabozantinib for differentiated thyroid cancer". U.S. Food and Drug Administration (FDA). 22 September 2021. Retrieved 22 September 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  19. ^ Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, et al. (December 2011). "Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth". Molecular Cancer Therapeutics. 10 (12): 2298–2308. doi:10.1158/1535-7163.MCT-11-0264. PMID 21926191. S2CID 16709393.
  20. ^ "Cabozantinib Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 29 November 2010. Retrieved 11 November 2020.
  21. ^ "Search Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 2 March 2017. Retrieved 11 November 2020.
  22. ^ "Thyroid cancer drug cabozantinib prolongs PFS". Archived from the original on 2012-04-02. Retrieved 24 October 2011.
  23. ^ Garde D (March 1, 2016). "Ipsen bets up to $855M on Exelixis' once-failed cancer drug". FierceBiotech.
  24. ^ "FDA approves cabozantinib for hepatocellular carcinoma". U.S. Food and Drug Administration (FDA). 14 January 2019. Retrieved 23 September 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  25. ^ "Search of: cabozantinib | Recruiting, Active, not recruiting, Enrolling by invitation Studies - List Results - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2021-08-09.
  26. ^ Fisher MJ, Shih CS, Rhodes SD, Armstrong AE, Wolters PL, Dombi E, et al. (January 2021). "Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial". Nature Medicine. 27 (1): 165–173. doi:10.1038/s41591-020-01193-6. PMC 8275010. PMID 33442015.

Further reading

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[edit]
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