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:

Renal cell carcinoma (RCC):

Single drug therapy for advanced renal cell carcinoma patients

Combination therapy with nivolumab as first-line treatment for advanced RCC

Hepatocellular carcinoma (HCC): treatment for hepatocellular carcinoma patients who have received sorafenib

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

Neuroendocrine tumors (NETs): Treatment of locally advanced or metastatic unresectable 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

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

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: May cause fatal bleeding, patients with recent bleeding history should not use it

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

Thrombotic event: Immediate discontinuation of medication is required for myocardial infarction

Hypertension crisis: Regular monitoring of blood pressure during treatment

Hepatotoxicity: More common when combined with nivolumab

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

Jaw necrosis: oral examination is required before treatment

4、 Medication for special populations

Pregnant women: May cause fetal damage, contraception is required during medication and within 4 months of discontinuation

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

Children over 12 years old 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 using strong CYP3A4 inhibitors (such as ketoconazole) or inducers (such as rifampicin) in combination. The combination with proton pump inhibitors requires a 4-hour interval.

6、 Clinical data

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

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

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

Cabozantinibinformation