Cabocantinib

Cabozantinib is a so-called multikinase inhibitor. The active substance inhibits the tyrosine kinase c-Met and the VEGF receptor-2. This mechanism leads to an inhibition of tumor growth and also of metastasis formation. Cabozantinib (Cabometyx) can be used for:

• advanced renal cell carcinoma (RCC) for first-line treatment of adult patients at intermediate or high risk; in adults after previous targeted therapy against VEGF or in combination with nivolumab for first-line treatment
• Hepatocellular carcinoma (HCC) in adults previously treated with sorafenib.
• Differentiated thyroid carcinoma (DTC) as monotherapy for the treatment of adults who are refractory to or ineligible for radioiodine (RAI) and who have experienced progression during or after prior systemic therapy.

Cabozantinib has a long half-life of 55 hours

at steady state the clearance is 4.4 l/hour

Elimination mainly through the faeces (54%) and urine (27%)

After oral administration, the peak plasma concentration is reached after about 2-5 hours

Plasma protein binding ≥ 99.7%

There are no studies on the use of cabozantinib in pregnant women. Animal experiments have shown that cabozantinib may have embryofetal and teratogenic effects. However, it is not known whether the potential risk also applies to humans. Therefore, cabozantinib should not be used during pregnancy unless treatment is absolutely necessary due to the clinical condition of the woman.

It is not known whether cabozantinib and/or its metabolites pass into breast milk. For this reason, mothers should not breastfeed during treatment with cabozantinib and for at least 4 months after completion of therapy to avoid potential risks to the baby.

The very common side effects include:

• anemia
• hypothyroidism
• Metabolic and nutritional disorders, weight loss
• Headaches, dizziness
• hypertension

VEGFR inhibitors cause a wide range of dermatologic conditions that have been described as class effects (Soto-Garcia D et al.2024). These toxicities include:

• Hand-foot reactions
• alopecia
• generalized depigmentation of skin and/or hair
• pruritus
• xerosis of the skin
• acneiform skin rashes
• scrotal erythema
• subungual splinter hemorrhages.

Less common are:

• mucositis and the
• reactive perforating collagenosis (usually associated with chronic renal insufficiency and diabetes mellitus.

Special precautions must be taken for:

• Patients with Crohn's disease, ulcerative colitis, peritonitis, diverticulitis or appendicitis
• patients at risk of thromboembolism or bleeding
• severe hypertension
• multiple symptoms, including seizures, headaches, visual disturbances, confusion or altered mental function (suspected RPLS)
• Risk of QT prolongation
• CYP3A4 inducers and inhibitors
• Drugs for the binding of bile salts
• P-glycoprotein substrates (e.g. fexofenadine, aliskiren, ambrisentan, dabigatran etexilate, digoxin, colchicine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol, tolvaptan)
• Therapy with MRP2 inhibitors (Note: MRP2 inhibitors block the activity of the multidrug resistance protein 2 (MRP2) transporter. MRP2 is a protein that transports various compounds, including drugs and toxins, from the cells into the bile. Known MRP2 inhibitors include, for example, probenecid and ciclosporin. In addition, certain flavonoids such as quercetin and baicalein as well as some antiretroviral drugs have been shown to inhibit MR Ciclosporin, Efavirenz, Emtricitabine).

The drug should not be used in cases of proven hypersensitivity reactions to cabozatinib.

Präpa: Preparations of ATC group L01EX07 - Cabozantinib

CABOMETYX® 20 mg film-coated tablets Ipsen Pharma GmbH

Cabometyx 20 mg Medicopharm Film-coated tablets Medicopharm AG

CABOMETYX® 40 mg film-coated tablets Ipsen Pharma GmbH

Cabometyx 40 mg Medicopharm film-coated tablets Medicopharm AG

Wound healing disorders have been observed in patients treated with cabozantinib, which is why treatment should be stopped at least 28 days before a planned operation.

As the active substance is associated with triggering proteinuria, urine should be checked regularly during treatment.

1. Abou-Alfa GK et al. (2018) Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med 379:54-63.
2. Chan JA et al. (2025) Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors. N Engl J Med 392:653-665.
3. Soto-García D et al. (2024) Acquired perforating dermatoses and cabozantinib: A novel cutaneous toxicity. J Dtsch Dermatol Ges 22:594-596.