About - Cabometyx EU

What are the CABOMETYX® indications?

CABOMETYX^® is indicated for the treatment of advanced renal cell carcinoma (RCC):¹

In treatment-naïve adults with intermediate or poor risk
In adults following prior vascular endothelial growth factor (VEGF)-targeted therapy

CABOMETYX^®is also indicated as monotherapy for the treatment of hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib.¹

Learn more about CABOMETYX® in HCC →

Indications

What is the mechanism of action of CABOMETYX®?

CABOMETYX^®is a small molecule tyrosine kinase inhibitor that simultaneously inhibits multiple receptor tyrosine kinases implicated in RCC pathogenesis.¹These include:

Vascular endothelial growth factor receptor (VEGFR)¹

RCC is a VEGF-driven disease and one of the most hypervascularised tumour types^2-3
VEGFR promotes tumour angiogenesis and tumour growth^2-3

Hepatocellular growth factor receptor protein (MET)¹

Dysregulation of MET is implicated in tumour development, invasion, and angiogenesis⁴

Gas6 receptor (AXL)¹

AXL promotes tumour progression^5-6
Inactivation of AXL reverses the invasive and metastatic phenotype of clear cell RCC⁵

Mechanism of action

CABOMETYX^® has a unique mechanism of action by inhibiting VEGFR as well as MET and AXL, the latter two of which are not inhibited by other tyrosine kinase inhibitors.¹

CABOMETYX® mechanism of action in RCC

_{Adapted from SmPC}¹

For further information of the mechanism of action of CABOMETYX^®, please refer to Section 5.1 of the Summary of Product Characteristics (SmPC).¹

What are the dosing recommendations for CABOMETYX®?

The recommended dose for CABOMETYX^® is 60 mg orally, once daily. Treatment should continue until it is no longer clinically beneficial or unacceptable toxicity occurs. Dosing can be adjusted to match patient therapy requirements as outlined below.¹

When taking CABOMETYX^® patients should be given the following advice¹:

A missed dose should not be taken if it is less than 12 hours before the next dose.¹

As most adverse events occur early in the course of CABOMETYX^® therapy, patients should be evaluated closely during the first 8 weeks of treatment to determine if dose modifications are necessary.¹

Can I reduce the dose?

Dosing can be adjusted to match patient therapy requirements.¹

It may be necessary to temporarily interrupt and/or reduce the dose of CABOMETYX^® therapy if managing a suspected adverse drug reaction.¹

If required, the following dose reductions can be used¹:

Recommended dose – 60 mg once daily
First reduction – 40 mg once daily
Second reduction – 20 mg once daily

Recommended CABOMETYX^® dose modifications for adverse reactions¹

	Treatment modification
Adverse reaction and severity	Continue treatment	Dose reduction	Supportive care
Grade 1 & 2 Tolerable and easily managed	Yes	Usually not required	Consider adding as indicated
Grade 2 Intolerable and cannot be managed with a dose reduction or supportive care	Interrupt until resolution to Grade ≤1	Consider reinitiating at reduced dose	Add as indicated
Grade 3 Except clinically non-relevant laboratory abnormalities	Interrupt until resolution to Grade ≤1	Reinitiate at reduced dose	Add as indicated
Grade 4 Except clinically non-relevant laboratory abnormalities	Interrupt treatment Institute appropriate medical care	If adverse reaction resolves to Grade ≤1, re-initiate at a reduced dose. If adverse reaction does not resolve, permanently discontinue CABOMETYX.

_{Adapted from SmPC¹}

For further information on dosing recommendations, including dose modifications, dose interruptions and use in special populations, please refer to Section 4.2 of the SmPC.¹

Dosing

What are the adverse drug reactions of CABOMETYX®?

Adverse reactions reported in patients treated with CABOMETYX®

MedDRA system organ class*	Very common (≥1/10)	Common (≥1/100 to <1/10)
Infections and infestations		Abscess
Blood and lymphatic disorders	Anaemia Thrombocytopaenia	Neutropenia Lymphopenia
Endocrine disorders	Hypothyroidism
Metabolism and nutrition disorders	Decreased appetite Hypomagnesaemia Hypokalaemia Hypoalbuminaemia	Dehydration Hypophosphataemia Hyponatraemia Hypocalcaemia Hyperkalaemia Hyperbilirubinemia Hyperglycaemia Hypoglycaemia
Nervous system disorders	Dysgeusia Headache Dizziness	peripheral neuropathy (including sensory)
Ear and labyrinth disorders		Tinnitus
Vascular disorders	Hypertension Haemorrhage	Deep vein thrombosis Venous thrombosis Arterial thrombosis
Respiratory, thoracic, and mediastinal disorders	Dysphonia Dyspnoea Cough	Pulmonary embolism
Gastrointestinal disorders	Diarrhoea Nausea Vomiting Stomatitis Constipation Abdominal pain Dyspepsia Upper abdominal pain	Gastrointestinal perforation Fistula Gastro-oesophageal reflux disease Haemorrhoids Oral pain Dry mouth Dysphagia, glossodynia
Skin and subcutaneous tissue disorders	PPES Rash	Pruritus Alopecia Dry skin Dermatitis acneiform Hair colour change Hyperkeratosis
Musculoskeletal and connective tissue disorders	Pain in extremity	Muscle spasms Arthralgia
Renal and urinary disorders		Proteinuria
General disorders and administration site conditions	Fatigue Mucosal inflammation Asthenia Peripheral oedema
Investigations	Weight decreased Serum ALT, AST, ALP increased Hepatic encephalopathy	Blood bilirubin increased Creatinine increased Triglycerides increased GGT increased Amylase increase Blood cholesterol increased Lipase increased Hepatobiliary disorders

_{*Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness}

_{ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, Gamma-glutamyl transferase; PPES, palmar-plantar erythrodysaesthesia syndrome}

_{Adapted from SmPC¹}

Adverse events

Management of adverse reactions

Management of suspected adverse drug reactions may require temporary treatment interruption and/or dose reduction of CABOMETYX^®therapy (see ‘What are the dosing recommendations for CABOMETYX^®?’ above and Table 1 in Section 4.2 of the SmPC). When dose reduction is necessary, it is recommended to reduce to 40 mg daily, and then to 20 mg daily. Dose interruptions are recommended for management of common terminology criteria for adverse events (CTCAE) grade 3 or greater toxicities or intolerable grade 2 toxicities. Dose reductions are recommended for events that, if persistent, could become serious or intolerable.¹

Description of selected adverse reactions

Data for the following reactions are based on patients who received cabozantinib 60 mg once daily, orally in the pivotal studies in RCC following prior VEGF-targeted therapy and in treatment-naïve RCC and in HCC following prior systemic therapy.¹

Gastrointestinal (GI) perforation

In the METEOR study, conducted in patients with RCC who had reeceived prior VEGF-targeted therapy, GI perforations were reported in 0.9% (3/331) of cabozantinib-treated RCC patients. Events were Grade 2 or 3. Median time to onset was 10.0 weeks.¹

In the CABOSUN study, conducted in previously untreated RCC patients, GI perforations were reported in 2.6% (2/78) of cabozantinib-treated patients. Events were Grade 4 and 5.¹

In the CELESTIAL study conducted in patients with HCC, GI perforations were reported in 0.9% of cabozantinib-treated patients (4/467). All events were Grade 3 or 4. Median time to onset was 5.9 weeks.¹

Fatal perforations have occurred in the cabozantinib clinical programme.¹

Hepatic encephalopathy

In the CELESTIAL study, hepatic encephalopathy (hepatic encephalopathy, encephalopathy, hyperammonaemic encephalopathy) was reported in 5.6% of cabozantinib-treated patients (26/467); Grade 3-4 events in 2.8%, and one (0.2%) Grade 5 event. Median time to onset was 5.9 weeks.¹

No cases of hepatic encephalopathy were reported in the RCC studies (METEOR and CABOSUN).¹

Diarrhoea

In the METEOR study, diarrhoea was reported in 74% of cabozantinib-treated RCC patients (245/331); Grade 3-4 events in 11%. Median time to onset was 4.9 weeks.¹

In the CABOSUN study, diarrhoea was reported in 73% of cabozantinib-treated patients (57/78);Grade 3-4 events in 10%.¹

In the CELESTIAL study, diarrhoea was reported in 54% of cabozantinib-treated patients (251/467); Grade 3-4 events in 9.9%. Median time to onset of all events was 4.1 weeks. Diarrhoea led to dose modifications, interruptions and discontinuations in 84/467 (18%), 69/467 (15%) and 5/467 (1%) of subjects, respectively.¹

Fistulas

In the METEOR study, fistulas were reported in 1.2% (4/331) of cabozantinib-treated patients and included anal fistulas in 0.6% (2/331) cabozantinib-treated patients. One event was Grade 3; the remainder was Grade 2. Median time to onset was 30.3 weeks.¹

In the CABOSUN study, no cases of fistulas were reported.¹

In the CELESTIAL study, fistulas were reported in 1.5% (7/467) of the HCC patients. Median time to onset was 14 weeks.¹

Fatal fistulas have occurred in the cabozantinib clinical programme.¹

Haemorrhage

In the METEOR study, the incidence of severe haemorrhagic events (Grade ≥ 3) was 2.1% (7/331) in cabozantinib-treated RCC patients. Median time to onset was 20.9 weeks.¹

In the CABOSUN study, the incidence of severe haemorrhagic events (Grade ≥ 3) was 5.1% (4/78) in cabozantinib-treated RCC patients.¹

Fatal haemorrhages have occurred in the cabozantinib clinical programme.¹

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

No case of RPLS was reported in the METEOR, CABOSUN or CELESTIAL studies, but RPLS has been reported rarely in other clinical studies (in 2/4,872 subjects; 0.04%).¹

Reporting of suspected adverse reactions

To report an adverse event, please fill in our contact form contact form

For information on the adverse events associated with CABOMETYX^®, please refer to Section 4.8 of the SmPC.¹

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