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Cabozantinib

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Cabozantinib

Cabozantinib_FR

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Medically reviewed

Laura Arias

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Cabozantinib

Property Description
Active ingredient Cabozantinib (as malate salt)
Form Oral tablet
Pharmacological class Multi-Target Receptor Tyrosine Kinase (RTK) Inhibitor
General Purpose Targeted antineoplastic agent
Origin Synthetic compound

What Type of Medicine is Cabozantinib?

Cabozantinib is a highly specialized, synthetic compound that is classified pharmacologically as a Multi-Target Receptor Tyrosine Kinase (RTK) Inhibitor. It belongs to the broader category of antineoplastic agents, which are drugs generally focused on impeding the progression of severe cellular dysfunctions.

This small molecule drug is an example of modern targeted therapy, meaning its mechanism is specifically engineered to interact with precise molecular structures. The active ingredient itself is Cabozantinib, typically administered as the salt, Cabozantinib malate. A key differentiating factor for Cabozantinib among other multi-kinase inhibitors is its ability to simultaneously block the MET, VEGFR2, and RET pathways, which are molecular targets associated with cell growth and resistance.

What are the Components and Form of Cabozantinib?

The medication is a single-ingredient product featuring Cabozantinib malate as its active component, and it is available as a prescription-only oral tablet for systemic administration. The oral route of administration ensures the medicine is taken by mouth to be absorbed into the bloodstream.

This pharmaceutical preparation is manufactured using solid pharmaceutical excipients to create a stable dosage form that allows for reliable systemic delivery of the active substance. The manufacturing process is designed to ensure established quality and consistency of the tablet form across various strengths.

How Does Cabozantinib Generally Function?

Cabozantinib's fundamental physiological action is the targeted inhibition of multiple Receptor Tyrosine Kinases (RTKs). By blocking these signaling cascades, the compound provides a comprehensive, dual therapeutic purpose: it disrupts the internal machinery driving uncontrolled cellular division and simultaneously limits the formation of new blood vessels needed to sustain and spread the problematic tissue (anti-angiogenesis).

This dual molecular interference is why Cabozantinib is used as a targeted therapeutic option when suppressing the systemic advancement of abnormal cellular activity is the medical objective. By addressing multiple targets at once, the medicine helps to prevent certain resistance mechanisms that can arise with inhibitors focused on a single pathway.

Regulatory References

  1. DrugBank
  2. European Medicines Agency [EMA]

What side effects are possible with Cabozantinib?

Possible Side Effects and Safety Information

The official safety profile for Cabozantinib, a multi-target receptor tyrosine kinase inhibitor, is organized into categories based on frequency and affected body systems, as documented by governmental regulatory authorities like the FDA and EMA.

Frequency-Classified Adverse Reactions

The regulatory label identifies many adverse effects, with certain events classified as Very Common (ge 1/10). These include Diarrhea, Fatigue, Decreased appetite, Hypertension (high blood pressure), and Palmar-Plantar Erythrodysesthesia Syndrome (PPES). Other common events include Proteinuria, Thromboembolic events, and Hemorrhage. Certain reactions, such as Osteonecrosis of the Jaw (ONJ) and non-gastrointestinal fistulas, are officially documented as Uncommon.

Serious Adverse Reactions and Systemic Concerns

Specific risks are highlighted due to their clinical significance, encompassing Gastrointestinal Perforations and Fistulas, severe and fatal Hemorrhage, and serious arterial or venous Thromboembolic Events (e.g., pulmonary embolism). Other documented concerns include Hypertensive Crisis, Hepatotoxicity (severe liver enzyme elevations), and Reversible Posterior Leukoencephalopathy Syndrome (RPLS). Effects are classified across several System-Organ Classes, including Gastrointestinal Disorders, Vascular Disorders, and Metabolism and Nutrition Disorders.

Safety Restrictions and Special Population Notes

The official safety documents note certain administration-agnostic restrictions. For example, the medicine should not be initiated in patients with uncontrolled hypertension or a recent history of severe hemorrhage. Treatment must also be withheld prior to scheduled surgery due to the risk of impaired wound healing. Furthermore, the label advises specific caution for patients with hepatic impairment, with use not recommended in severe cases, and women of reproductive potential are advised of the risk of embryo-fetal toxicity.

Overdose and Emergency Response

Overdose and when to seek help

The official regulatory documents state that a Cabozantinib overdose is primarily manifested as exaggerated known adverse reactions or toxicities, rather than a unique set of symptoms. In situations of overexposure, immediate medical attention is required, as the physiological consequences can be severe or life-threatening.

Urgent Medical Help is Required

The need to seek immediate medical attention is explicitly mandated upon the development of specific, severe conditions. These critical regulatory triggers include Grade 3 or Grade 4 hemorrhage, Gastrointestinal perforation, formation of a Grade 4 fistula, acute myocardial infarction, other serious arterial or venous thromboembolic events, a hypertensive crisis, or Reversible Posterior Leukoencephalopathy Syndrome (RPLS). The regulatory standard for these life-threatening events is the permanent discontinuation of the medication.

Management and Monitoring

There is no specific antidote known for Cabozantinib overdose according to the official prescribing information. Management is therefore limited to providing symptomatic and supportive treatment. In the event of severe toxicities (Grade 3), regulatory guidelines require that the medication be withheld and closely monitored until the condition resolves or improves to a safe level (Grade leq 1 or baseline). The monitoring includes close observation of the individual's blood pressure and clinical laboratory parameters until resolution.

Therapeutic Uses of Cabozantinib

Cabozantinib Quick Facts

  • Therapeutic Domain: Advanced Renal Cell Carcinoma (RCC)
  • Therapeutic Domain: Previously Treated Hepatocellular Carcinoma (HCC)
  • Therapeutic Domain: Differentiated Thyroid Cancer (DTC) in specific patients
  • Therapeutic Domain: Previously Treated Neuroendocrine Tumors (NETs) in adults and certain pediatric patients

What Cabozantinib Treats: Main Uses and Benefits

Cabozantinib is an approved treatment option for managing several types of advanced or progressive cancers. It is used to address advanced renal cell carcinoma (RCC) and, in certain regimens, as a first-line treatment for advanced RCC when used in combination with another medication.

For liver cancer, this medication is indicated for use in people with hepatocellular carcinoma (HCC) who have previously received treatment with sorafenib.

Cabozantinib is also a therapeutic option for adult and pediatric patients (12 years of age and older) with differentiated thyroid cancer (DTC) that has progressed following prior therapy and who are radioactive iodine-refractory or ineligible.

Furthermore, this treatment is indicated for adult and pediatric patients (12 years and older) with previously treated, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and extra-pancreatic neuroendocrine tumors (epNET).

Eligibility and Restrictions for Use

Cabozantinib is an approved treatment option for adult patients across all labeled indications. In the pediatric population, it is specifically permitted for use in adolescents aged 12 years and older who have Differentiated Thyroid Cancer or certain Neuroendocrine Tumors. Use is not recommended in children under 12 years of age, as safety and efficacy have not yet been established in this younger group.

The medicine is contraindicated for any patient with a known hypersensitivity to Cabozantinib or any of its excipients. Furthermore, eligibility is strictly limited by specific physiological and clinical conditions. Cabozantinib is not recommended for patients with severe hepatic impairment (Child-Pugh C) or severe renal impairment due to a lack of established safety data in these populations.

Treatment must not be administered to patients with uncontrolled hypertension or a recent history of severe hemorrhage. Women who are pregnant or breastfeeding are advised to avoid use due to the risk of fetal harm and transfer. Additionally, treatment must be temporarily withheld for a period before and after any major surgery or invasive dental procedure until adequate wound healing is confirmed.

What should I know about interactions with other medicines?

Interactions with other medicines and products

Official regulatory information for Cabozantinib details specific interaction patterns based on how the body processes the medicine. Cabozantinib is primarily a substrate of the Cytochrome P450 3A4 (CYP3A4) enzyme, which is the mechanistic basis for most pharmacokinetic interactions.

Pharmacokinetic Interaction Constraints

Substance Category Formal Outcome / Restriction
Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin) Increase Cabozantinib exposure; co-administration requires dose modification to manage the elevated levels.
Strong CYP3A4 Inducers (e.g., Rifampin, Phenytoin, St. John's Wort) Decrease Cabozantinib exposure significantly; chronic co-administration must be avoided due to reduced drug effectiveness.

Non-Drug and Population Restrictions

  • Food and Drink: Cabozantinib exposure increases when taken with food. Official labeling mandates administration on an empty stomach, specifically at least one hour before or two hours after eating. Consumption of Grapefruit or Grapefruit Juice may also increase plasma concentrations.
  • Pharmacodynamic Effects: Co-administration with the antineoplastic agent Nivolumab is associated with an officially documented increased incidence of liver enzyme elevations (Hepatotoxicity).
  • Hepatic Impairment: Patients with moderate hepatic impairment (Child-Pugh B) require a mandatory dose reduction due to officially documented altered clearance and increased exposure. Use in severe hepatic impairment (Child-Pugh C) is not recommended.

Mechanism of Action

How Cabozantinib Works

Cabozantinib functions as a small molecule tyrosine kinase inhibitor that modulates multiple cellular signaling pathways. Its primary mechanism involves the inhibition of several receptor tyrosine kinases (RTKs), specifically including MET and RET.

Inhibiting Excessive Growth Signals

The binding of Cabozantinib prevents the phosphorylation and activation of RTKs like MET and RET. This inhibition disrupts the downstream intracellular cascade responsible for initiating uncontrolled cellular multiplication and survival signaling, resulting in the modulation of cellular proliferation rates.

Altering Vascular Support

The drug also targets and blocks Vascular Endothelial Growth Factor Receptors (VEGFR1, 2, and 3) on endothelial cells. By inhibiting these receptors, Cabozantinib disrupts the required signaling for the formation of new blood vessels (angiogenesis). This process modulates the tissue's vascular support, affecting its access to nutrients and oxygen.

Modulating the Tissue Microenvironment

Furthermore, Cabozantinib inhibits RTKs such as AXL and KIT, which are expressed on various cells within the tissue microenvironment. The inhibition of these targets disrupts survival cues and cell communication within the local cellular environment, contributing to the overall modulation of pathway activity.

Dosage and Administration Information

Cabozantinib is administered orally as a film-coated tablet and is used on a continuous, once-daily schedule. The tablets are available in multiple strengths, including 20 mg, 40 mg, and 60 mg, which facilitates precise dosage adjustments. The tablet and capsule formulations of cabozantinib are not interchangeable.

Standard Administration Principles

The standard starting dosage for monotherapy across multiple indications is 60 mg once daily. For its use in combination regimens, the starting dose is typically 40 mg once daily. Administration must occur on an empty stomach, meaning the tablet must be taken at least one hour before eating or at least two hours after consuming food.

Key Use Constraints

The tablet must be swallowed whole and is not to be crushed, chewed, or split. If a dose is missed, instructions advise against taking it if the next scheduled dose is less than 12 hours away. Treatment is typically continued until a loss of clinical benefit or the emergence of intolerance, with instructions detailing the sequence of dose reduction steps if needed. For patients with moderate hepatic impairment (Child-Pugh B), the labeled starting dose is reduced to 40 mg once daily. The therapy requires temporary suspension, or withholding, for a minimum of three weeks prior to any planned elective surgical procedure.

Recent Clinical Evidence

Cabozantinib: Recent Clinical Evidence

This section outlines the types of clinical research conducted for Cabozantinib, focusing on the large-scale, randomized studies that have explored its use in various advanced cancers. The information describes the study designs and what was measured, but does not offer medical advice or promises about individual outcomes.

Evidence for use in Advanced Kidney Cancer (Renal Cell Carcinoma)

The research exploring Cabozantinib in advanced RCC includes several randomized trials. The METEOR trial studied Cabozantinib against the comparator Everolimus in previously treated patients, where measurements of Overall Survival (OS) and Progression-Free Survival (PFS) were numerically higher for the Cabozantinib group. For first-line RCC, the CheckMate 9ER trial studied Cabozantinib in combination with Nivolumab against Sunitinib, with research describing PFS and OS measurements that were also numerically higher for the combination.

Evidence for use in Other Advanced Cancers

For previously treated Hepatocellular Carcinoma (HCC), the CELESTIAL trial compared Cabozantinib to placebo. Research described median measurements for both OS and PFS that were numerically higher for the Cabozantinib group.

For progressive Differentiated Thyroid Cancer (DTC), the COSMIC-311 trial compared Cabozantinib to placebo in patients refractory to radioactive iodine. Research reported median PFS measurements that were numerically higher for the Cabozantinib group.

For previously treated Neuroendocrine Tumors (NETs), the CABINET trial studied Cabozantinib against placebo, with research describing median PFS measurements that were numerically higher across both pancreatic and extra-pancreatic tumor types.

Research Gaps and Follow-up

The majority of evidence relies on high-level randomized studies. Research exploring the use in pediatric patients (12 years and older) was included in the studies for DTC and NETs. However, data for patients with significant liver function impairment remain limited. For indications approved based on interim analyses (such as DTC and NETs), the final, long-term measurements for Overall Survival are still maturing.

Key Studies & References

  1. Final results from CABINET Phase III trial reinforce efficacy benefits of Cabometyx® in advanced neuroendocrine tumors

Frequently Asked Questions (FAQ)

Common questions about Cabozantinib (FAQ)

Q: How long will I need to take Cabozantinib?

A: Official regulatory documents indicate that treatment with Cabozantinib is typically continued until the patient no longer experiences a clinical benefit from the drug or until they experience side effects, known as unacceptable toxicity, that require stopping the medicine. The continuation of therapy is managed by a healthcare provider based on the patient's individual response and tolerance.

Q: Does Cabozantinib cause hair loss?

A: While regulatory information for the Cabozantinib tablet formulation does not list hair loss as an adverse reaction, a change in hair color has been reported as a common side effect in official documents for the capsule formulation of the same active ingredient. Concerns about changes to hair should be discussed with a healthcare professional.

Q: How long does it take for Cabozantinib to start working?

A: The official product information does not specify a timeline for when the medicine first starts to work. However, in clinical studies, researchers measure how long patients who responded to the drug continue to benefit. For example, in Differentiated Thyroid Cancer trials, the median Duration of Response—the length of time a tumor response is maintained—was reported to be around 14.6 months.

Q: Can men and women use Cabozantinib while trying to conceive?

A: Based on how the drug works and findings in animal studies, Cabozantinib may cause harm to an unborn baby (fetal harm) and may impair fertility (the ability to become pregnant) in both men and women. Regulatory labeling indicates that effective contraception is required for female patients of reproductive potential and for female partners of male patients during treatment and for at least 4 months following the final dose, due to the potential for fetal harm.

Q: How is Cabozantinib removed from the body (e.g., kidneys, liver)?

A: The body processes Cabozantinib primarily in the liver, where it is broken down by an enzyme system called CYP3A4. The medicine and its breakdown products (metabolites) are mostly removed from the body through fecal elimination (via the feces), rather than through the kidneys.

Q: How often will I need to get blood tests while on Cabozantinib?

A: Official regulatory documents advise that patients will need regular monitoring with blood and urine tests. Specifically, liver enzymes (ALT and AST) should be checked before starting treatment and periodically throughout the course of therapy. Protein levels in the urine should also be regularly monitored as part of therapy.

How should Cabozantinib be stored and disposed of?

Storage and Disposal of Cabozantinib

The official labeling for cabozantinib strictly defines the mandatory conditions for storage and disposal to ensure product integrity and safety.

Storage Requirements

Cabozantinib must be kept at controlled room temperature, typically defined as 20 C to 25 C. The medicine must be protected from environmental factors, specifically by keeping it away from heat, moisture, and freezing temperatures. It must be stored in its original container with the container kept closed. A critical requirement is to store the medicine out of the reach and sight of children.

Disposal Instructions

To prevent environmental contamination, cabozantinib must not be thrown away in household waste or flushed down the toilet. Patients are instructed to consult a pharmacist or healthcare professional for guidance on the proper disposal of any unused or expired product, following local pharmaceutical waste regulations. The medicine should not be used after the expiry date.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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