Cabozantinib is a multi-target tyrosine kinase inhibitor (TKI) that selectively inhibits the activity of receptor tyrosine kinases such as MET, VEGFR-1/2/3, AXL, RET, ROS1, etc., blocking tumor angiogenesis, inhibiting tumor cell proliferation and metastasis.

1、 Indications

Cabozantinib is a multi-target tyrosine kinase inhibitor suitable for the following situations:

1. Renal cell carcinoma (RCC): monotherapy combined with nivolumab as first-line treatment for advanced RCC patients

2. Hepatocellular carcinoma (HCC): Treatment for hepatocellular carcinoma patients who have received sorafenib before

3. Differentiated thyroid cancer (DTC): Treatment for locally advanced or metastatic DTC patients aged 12 years and above who are refractory or unsuitable for radioactive iodine therapy, and who have previously undergone VEGFR targeted therapy and have progressed

4. Neuroendocrine tumors (NETs): Treatment for unresectable locally advanced or metastatic pancreatic (pNET) or extrapancreatic (epNET) highly differentiated neuroendocrine tumors aged 12 years and older who have previously received treatment

2、 Usage and dosage specifications

Standard dose:

Adults and adolescents weighing ≥ 40kg: 60mg orally once daily (monotherapy)

Combined with nivolumab: 40mg once daily

Teenagers weighing less than 40kg: 40mg once daily

Medication requirements: Take on an empty stomach (1 hour before or 2 hours after meals), swallow the whole tablet and do not crush/chew it

Dose adjustment:

Gradually reduce to 40mg or 20mg once daily according to the severity of adverse reactions

Serious adverse reactions require permanent discontinuation of medication

Surgical management: Stop medication 3 weeks before surgery, and resume medication at least 2 weeks after surgery and wound healing

Omission treatment: If the missed dose exceeds 12 hours, skip the dose and take the medication normally the next day

3、 Side effects and precautions

Common adverse reactions (≥ 20%):

Single drug treatment: diarrhea, fatigue, skin reactions on hands and feet, decreased appetite, hypertension, nausea, vomiting, weight loss

Combination therapy: diarrhea, fatigue, hepatotoxicity, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain

Serious risk warning:

Bleeding risk: There may be fatal bleeding, and patients with a recent history of bleeding should avoid using it.

Perforation/fistula: Monitor gastrointestinal symptoms and seek medical attention immediately if abdominal pain occurs.

Thrombotic events, such as myocardial infarction, pulmonary embolism, etc., require immediate discontinuation of medication.

Hypertension crisis: Regularly monitor blood pressure during treatment, and adjust dosage if control is poor.

Hepatotoxicity: It is more common when combined with nivolumab and requires regular monitoring of liver function.

Wound healing disorders: Medication should be temporarily suspended before and after elective surgery.

Jaw necrosis: Oral examination is required before treatment, and treatment should be interrupted if jaw pain occurs.

Embryotoxicity: Pregnant women should avoid using it, and patients of childbearing age should take effective contraceptive measures.

4、 Medication for special populations

Pregnant women: May cause fetal damage, contraception is necessary during the medication period and 4 months after discontinuation.

Breastfeeding period: Breastfeeding is prohibited during the treatment period and within 4 weeks of discontinuation of medication.

Children: Adolescents aged 12 and above need to be monitored for bone growth.

Liver injury: Moderate liver injury should be reduced, and severe liver injury should be avoided.

5、 Drug interactions

Avoid combination use: strong CYP3A4 inhibitors (such as ketoconazole), strong/moderate CYP3A4 inducers (such as rifampicin).

Antacids: When used in combination with proton pump inhibitors, an interval of 4 hours (before) or 10 hours (after) is required.

6、 Clinical efficacy data

Renal cell carcinoma: median progression free survival (PFS) of 8.6 months with monotherapy and 16.6 months with combination therapy of nivolumab.

Hepatocellular carcinoma: median overall survival (OS) was 10.2 months (vs placebo 8.0 months).

Thyroid cancer: median PFS of 1.0 months (vs placebo of 1.9 months).

Neuroendocrine tumors: median PFSpNET 13.8 months, epNET 8.5 months.

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