Cabozantinib

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Cabozantinib.svg
Systematic (IUPAC) name
N-(4-((6,7-Dimethoxyquinolin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Clinical data
Trade names Cometriq
Licence data US FDA:link
Pregnancy cat.
Legal status
Routes Oral
Pharmacokinetic data
Protein binding ≥99.7%
Metabolism Hepatic (CYP3A4-mediated)
Half-life 55 hours
Excretion Faeces (54%), urine (27%)
Identifiers
CAS number 849217-68-1
ATC code None
ChemSpider 25948202
UNII 1C39JW444G
KEGG D10062
ChEBI CHEBI:72317 YesY
ChEMBL CHEMBL2105717
Synonyms XL184, BMS907351
Chemical data
Formula C28H24FN3O5 
Mol. mass 501.51 g mol

Cabozantinib (INN) (development code name XL184; marketed under the trade name Cometriq) is a small molecule inhibitor of the tyrosine kinases c-Met and VEGFR2, and has been shown to reduce tumor growth, metastasis, and angiogenesis.

It was developed by Exelixis Inc.

Cabozantinib was granted orphan drug status by the U.S. Food and Drug Administration (FDA) in January 2011.[1]

Cabozantinib was approved by the U.S. FDA in November 2012 for the treatment of medullary thyroid cancer.[2] It is currently undergoing clinical trials for the treatment of prostate, bladder, ovarian, brain, melanoma, breast, non-small cell lung, pancreatic, hepatocellular and kidney cancers.

Approvals and indications[edit]

In October 2011, cabozantinib met its primary endpoint in a phase 3 clinical trial (EXAM) conducted by Exelixis investigating its effect on progression-free survival in medullary thyroid cancer.[3] A new drug application was submitted in the first half of 2012,[4] and on November 29, 2012 cabozantinib was granted marketing approval by the U.S. FDA under the name Cometriq for treating patients with medullary thyroid cancer.[2]

Grapefruit and grapefruit juice should be avoided as they may increase the concentration of the drug in the blood.[5]

It is not yet known if cabozantinib is safe and effective in children.

Clinical trials[edit]

Glioblastoma multiforme[edit]

In 2009 a phase II study for relapsed glioblastoma multiforme reported encouraging interim results.[6]

Prostate cancer[edit]

Positive data from clinical trials in 2011 indicate cabozantinib is beneficial in metastatic advanced prostate cancer (castration-resistant prostate cancer). 97% of patients either had stabilization or improvement in bone malignancies. The median time to disease progression was 29 weeks.[7][8]

One US trial reported in May 2011: The best results were seen in patients with liver, prostate, and ovarian cancer: 22 of 29 patients with liver cancer, 71 of 100 patients with prostate cancer, and 32 of 51 with ovarian cancer experienced either partial tumor shrinkage or stable disease. Fifty-nine out of 68 patients who had bone metastases had their metastases shrink or disappear during the trial.[9]

It is undergoing clinical trials for the treatment of prostate, ovarian, brain, melanoma, breast, non-small cell lung, hepatocellular and kidney cancers.[10]

In 2014 [11] COMET-1, the phase 3 pivotal trial of cabozantinib in men with metastatic castration-resistant prostate cancer whose disease progressed after treatment with docetaxel as well as abiraterone and/or enzalutamide. The trial did not meet its primary endpoint of demonstrating a statistically significant increase in overall survival for patients treated with cabozantinib as compared to prednisone. Median progression free survival did exhibit a statistically significant improvement with 5.5 months for the Cabozantinib arm versus 2.8 months for the prednisone arm, but this did not translate to a statistically significant overall survival benefit at topline analysis; at that time the median OS for the cabozantinib arm of the trial was 11.0 months versus 9.8 months for the prednisone arm.

See also[edit]

References[edit]

External links[edit]