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Cabometyx: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on March 9, 2021.

1. How it works

  • Cabometyx is a brand (trade) name for cabozantinib which may be used for the treatment of certain cancers, such as renal cell carcinoma and hepatocellular carcinoma.
  • Cabometyx (cabozantinib) works by inhibiting tyrosine kinases. These are a family of enzymes that play a pivotal role in normal cellular communication and homeostasis( maintaining cell stability). Tyrosine kinases (TK) have been implicated in cancer development and progression. Usually, TK pathways prevent out-of-control cell proliferation and encourage apoptosis (the process of programmed cell death) of abnormal and old cells. In cancer cells, these TK pathways are often genetically or epigenetically modified to give cancer cells a selection advantage.
  • Cabometyx blocks or inhibits the activity of multiple tyrosine kinases, namely: MET, vascular endothelial growth factor (VEGFR)-1, -2 and -3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2. This inhibits the formation of new blood vessels that supply blood and nutrients to cancer cells and decreases the ability of tumors to spread (metastasize) to other parts of the body and invade surrounding tissues.
  • Cabometyx belongs to the class of medicines known as multikinase inhibitors. It may also be called a VEGF/VEGFR inhibitor.

2. Upsides

  • May be used for the first-line treatment of patients with advanced renal cell carcinoma (kidney cancer) in combination with nivolumab, or the treatment of advanced renal cell carcinoma.
  • May also be used to treat patients with hepatocellular carcinoma (liver cancer) who have previously been treated with Nexavar (sorafenib).
  • Taken orally (by mouth) once a day.
  • Available in 3 different strengths: 20mg (round tablet), 40mg (triangular tablet), 60mg (oval tablet).
  • No dosage reduction is required in people with mild to moderate renal impairment. There is no experience with using Cabometyx in severe renal impairment.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Gastrointestinal side effects (such as diarrhea, nausea, vomiting, mouth ulcers or inflammation, constipation, abdominal pain, or dyspepsia), fatigue, lack of energy, decreased appetite, and palmar-plantar erythrodysesthesia (hand-foot syndrome) are common side effects. High blood pressure, rash, weight loss, taste disturbances, hypothyroidism, hoarseness, cough, pain,, headache, and anemia are also common.
  • Diarrhea occurred in 63% of people treated with Cabometyx, including 11% with grade 3. Withhold until diarrhea improves to Grade 1 and resume at a reduced dose. Try to manage diarrhea with antidiarrheal treatments.
  • 44% of patients reported palmar-plantar erythrodysesthesia (PPE), including 13% with Grade 3 PPE. Withhold Cabometyx until improvement to Grade 1 then resume at a reduced dose.
  • High blood pressure was reported in 36% of patients, including hypertensive crises. Do not initiate in people with uncontrolled high blood pressure, and monitor blood pressure regularly throughout treatment. Withhold Cabometyx if BP is unable to be controlled then resume at a reduced dose once controlled.
  • Severe and fatal hemorrhages have occurred with Cabometyx (5% were classed as Grade 3 to 5). Do not administer Cabometyx to people with a history of hemorrhage and discontinue if Grade 3 or 4 hemorrhages occur.
  • Liver toxicity can occur when Cabometyx is used in combination with nivolumab. Monitor liver enzymes at baseline and throughout treatment. Withhold Cabometyx and nivolumab with elevated liver enzymes and consider treatment with corticosteroids.
  • Other serious side effects include adrenal insufficiency, osteonecrosis of the jaw, and reversible posterior leukoencephalopathy syndrome. Proteinuira has been reported and Cometyx should be discontinued in people who develop nephrotic syndrome.
  • Cabometyx can impair wound healing and should be withheld for at least 3 weeks before elective surgery and not administered until at least 2 weeks after major surgery.
  • 1% of people being treated with Cabometyx reported fistulas and gastrointestinal perforations, some of which were fatal. Monitor for abscesses and sepsis and discontinue if a grade 4 fistula or GI perforation occurs.
  • Increases the risk of potentially fatal thrombotic events, including venous thromboembolism and pulmonary embolism. Discontinue in patients who develop serious arterial or venous thromboembolic events or acute myocardial infarction.
  • Does not cure cancer. Delays the progression of cancer and increases survival.
  • The safety and effectiveness of Cabometyx in children has not been established.
  • Taken until cancer progression or intolerable side effects occur.
  • A dosage reduction is required in people with moderate hepatic impairment; avoid with severe hepatic impairment.
  • Although Caometyx contains the same generic as Cometriq (which is cabozantinib), Cabometyx tablets must not be substituted for the capsule form of Cometriq because it is a different formulation approved for the treatment of medullary thyroid cancer.
  • May cause harm to a developing fetus. Advise women not to become pregnant while taking Cabometyx and to use adequate contraception while taking Cabometyx and for 4 months after the last dose. Women should not breastfeed while taking Cabometyx and for 4 months after the final dose. Cabometyx may also impair fertility in females and males of reproductive potential.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Cabometyx is a multikinase inhibitor that decreases the ability of cancer cells to grow and spread and inhibits the formation of new blood vessels that supply blood and nutrients to the cancer cells. Diarrhea and palmar-plantar erythrodysesthesia are two common side effects, both of which require Cabometyx to be withheld if they are severe enough. Cabometyx may be used to treat renal cell or hepatocellular carcinoma.

5. Tips

  • Take Cabometyx exactly as directed by your doctor. Take each dose on an empty stomach, which means at least one hour before eating or at least two hours after eating.
  • Cabometyx is not suitable for everybody. tell your doctor if you have experienced any liver problems in the past, have a history of bleeding or have high blood pressure, or have had recent surgery.
  • Tell your doctor about any side effects that you experience with Cabometyx because some side effects require Cabometyx to be withheld until the side effect has improved. This includes side effects such as diarrhea and palmar-plantar erythrodysesthesia (hand-foot syndrome). Tell your doctor immediately if you experience any signs or symptoms of unusual severe bleeding or hemorrhage, persistent headaches, severe abdominal pain, shortness of breath, chest pain, leg swelling, severe nausea or vomiting, confusion, or yellow skin.
  • Cabometyx can impair wound healing and needs to be withheld at least 3 weeks before elective surgery and not administered until at least 2 weeks after major surgery. Tell all health professionals you are taking Cabometyx.
  • Keep good oral hygiene practices, such as brushing your teeth and flossing twice a day. See your healthcare provider if you develop mouth ulcers or inflammation, or jaw problems.
  • Tell your doctor or other health care provider about all the medicines you take, including prescription and over-the-counter (OTC) medicines, vitamins, and herbal supplements. Let them know if you eat grapefruit or drink grapefruit juice. Cabometyx interacts with several medicines and it may not be safe to take them together.
  • While taking Cabometyx you should use adequate contraception during treatment and for four months following the last dose to ensure you do not become pregnant. If you inadvertently become pregnant, tell your doctor immediately. Do not breastfeed while taking Cabometyx and for 4 months after the final dose. Cabometyx may also impair fertility in females and males of reproductive potential. Talk to your doctor about this.

6. Response and Effectiveness

  • Cabometyx (cabozantinib) is a tyrosine kinase inhibitor used to treat patients with advanced renal cell carcinoma or hepatocellular (liver) cancer.
  • At least three major trials have assessed the effectiveness of Cabometyx for the treatment of advanced renal cell carcinoma (METEOR, CABOSUN, CHECKMATE-9ER) and one trial investigated its use for the treatment of advanced hepatocellular carcinoma (CELESTIAL).
  • METEOR reported an average 7.4 months of progression-free survival (PFS) with Cabometyx compared with 3.8 months for everolimus. Overall survival (OS) was 21.4 months with Cabometyx and 16.5 months with everolimus.
  • CABOSUN reported a PFS of 8.6 months with Cabometyx compared to 5.3 months with everolimus.
  • CHECKMATE-9ER reported a PFS of 16.6 months with Cabometyx compared to 8.3 months with Sunitinib. The OS was not reached for either Cabometyx or sunitinib.
  • CELESTIAL reported a PFS of 5.2 months for Cabometyx versus 1.9 months for placebo. The OS was 10.2 months for Cabometyx versus 8 months for placebo.

7. Interactions

Medicines that interact with Cabometyx may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Cabometyx. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Cabometyx interacts with over 460 drugs and most of these interactions are considered moderate or major. Common medications that may interact with Cabometyx include:

  • agents used to treat constipation, such as bisacodyl, lactulose, or senna
  • albuterol
  • antibiotics, such as clarithromycin and ciprofloxacin
  • anticonvulsants, such as carbamazepine or phenytoin
  • antidepressants, such as amitriptyline, imipramine, nortriptyline, or SSRIs (eg, citalopram, fluoxetine, or paroxetine)
  • antifungals, such as itraconazole or ketoconazole
  • blood thinners and anticoagulants, such as apixaban, urokinase, or warfarin
  • chloroquine and hydroxychloroquine
  • cisapride
  • corticosteroids such as dexamethasone
  • CYP3A4 strong inhibitors (such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal, or grapefruit). Avoid or reduce the dosage of Cabometyx
  • CYP3A4 strong or moderate inducers (such as phenobarbital, phenytoin, rifampicin, rifabutin, St. John's Wort, or glucocorticoids [eg, dexamethasone]). Avoid or increase the dosage of Cabometyx
  • digoxin
  • duloxetine
  • herbals, such as echinacea
  • HIV medications such as indinavir and ritonavir
  • lithium
  • loperamide
  • mifepristone
  • magnesium salts
  • multiple sclerosis treatments such as fingolimod
  • NSAIDs such as diclofenac, ibuprofen, or flubriprofen
  • ondansetron
  • oxytocin
  • quinidine
  • rifampin and rifabutin
  • serotonin modulators, such as nefazodone and trazodone
  • some chemotherapy treatments
  • some heart medications, such as amiodarone
  • other medications used to treat mental illness, such as aripiprazole, clozapine and thioridazine.

Grapefruit juice and grapefruit products may increase the blood levels of Cabometyx and increase side effects such as diarrhea, nausea, and palmar-plantar erythrodysesthesia.

Note that this list is not all-inclusive and includes only common medications that may interact with Cabometyx. You should refer to the prescribing information for Cabometyx for a complete list of interactions.

References

Cabometyx (cabozantinib) Updated 01/2021. Exelixis, Inc. https://www.drugs.com/pro/cabometyx.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Cabometyx only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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