cabozantinib

Cabozantinib is used in two forms. A capsule form (Cometriq) is used to treat medullary thyroid cancer{{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}} and a tablet form (Cabometyx) is used to treat renal cell carcinoma, hepatocellular carcinoma, and differentiated thyroid carcinoma.{{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}}{{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}}

In the US, cabozantinib (Cabometyx) is indicated for the treatment of advanced renal cell carcinoma; advanced renal cell carcinoma, as a first-line treatment in combination with nivolumab; hepatocellular carcinoma for people who have been previously treated with sorafenib; and locally advanced or metastatic differentiated thyroid cancer that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.

In March 2025, the US Food and Drug Administration expanded the indication for cabozantinib (Cabometyx) to include the treatment of people aged twelve years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors; and for people aged twelve years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extra-pancreatic neuroendocrine tumors.{{cite press release | title=FDA Roundup: March 28, 2025 | website=U.S. Food and Drug Administration (FDA) | date=28 March 2025 | url=https://www.fda.gov/news-events/press-announcements/fda-roundup-march-28-2025 | access-date=28 March 2025}} {{PD-notice}}

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.

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). The black box also warns against the risk of uncontrolled bleeding. The tablet formulation (Cabometyx) warns of these effects as well.

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.

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.

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.

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.

Cabozantinib inhibits the following receptor tyrosine kinases (RTKs): c-Met (HGFR), VEGFR2, AXL, RET, and FLT3.{{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 }}

In 2023, the Institute for Clinical and Economic Review (ICER) identified Cabometyx (cabozantinib), developed by Exelixis, as one of five high-expenditure drugs that experienced significant net price increases without new clinical evidence to justify the hikes. Specifically, Cabometyx's wholesale acquisition cost rose by 7.5%, leading to an additional $86 million in costs to U.S. payers.{{Cite web |title=Institute for Clinical and Economic Review Announces Most Significant Drug-Price Hikes Unsupported by New Clinical Evidence in US |url=https://icer.org/news-insights/press-releases/icer-announces-most-significant-drug-price-hikes-unsupported-by-new-clinical-evidence-in-us/?mkt_tok=NjM4LVBYUi0zMTgAAAGYMxe5Fv3mzhJbiVnr0V4g2FUAcS3PgZOZSYRvQcW3_VFPXIet0TCD7bWAyVVeW2Q62e3AynO8rDpP8sIoIbs_qux8kQcMBBD4cDSe3Q |access-date=2025-02-06 |website=ICER |language=en-US}}

Cabozantinib was granted orphan drug status by the US Food and Drug Administration (FDA) in November 2010,{{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}} and in February 2017.{{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}}

Exelixis filed a new drug application with the FDA in 2012,{{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}} 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.{{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}}{{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 }} The capsule form was approved in the European Union for the same purpose in 2014.{{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}}

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

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

In December 2017, the FDA granted approval to cabozantinib (Cabometyx) for the treatment of people with advanced renal cell carcinoma (RCC).{{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}} 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.

In January 2019, the FDA approved cabozantinib (Cabometyx) for the treatment of people with hepatocellular carcinoma who have been previously treated with sorafenib.{{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}} 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.

In March 2025, the FDA approved cabozantinib (Cabometyx) for the treatment of people aged twelve years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET).{{cite web | title=FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET | website=U.S. Food and Drug Administration (FDA) | date=26 March 2025 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cabozantinib-adults-and-pediatric-patients-12-years-age-and-older-pnet-and-epnet | access-date=28 March 2025}} {{PD-notice}}

Cabozantinib is being researched{{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}} 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.{{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 }}

{{reflist}}

• {{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 }}

• {{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 | 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|NCT01865747|A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma (METEOR)}}
• {{ClinicalTrialsGov|NCT01908426|Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib (CELESTIAL)}}
• {{ClinicalTrialsGov|NCT03141177|A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 9ER)}}
• {{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|NCT03375320|Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors}}

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