About CABOMETYX® (cabozantinib)

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 →

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

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

_{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

Adverse reactions reported in patients treated with CABOMETYX®

_{*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}

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

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