Cabozantinib is a broad-spectrum, multi-target anti-tumor drug developed by Exelixis Biopharmaceuticals, Inc. While most anti-tumor drugs target 1-3 targets, cabozantinib targets more than 9, thus establishing its broad-spectrum anti-tumor activity.
Cabozantinib Indications
Cabozantinib is a multi-receptor tyrosine kinase inhibitor. Its FDA-approved indications include:
1. Medullary Thyroid Carcinoma
Cabozantinib capsules: Used to treat advanced, metastatic medullary thyroid carcinoma. Its efficacy is determined based on improvement in progression-free survival. Guidelines generally support the use of tyrosine kinase inhibitors, including cabozantinib, as first-line treatment for advanced and metastatic medullary thyroid carcinoma. The US FDA has designated it as an orphan drug for this purpose.
2. Differentiated Thyroid Cancer
Cabozantinib tablets: Used to treat locally advanced or metastatic differentiated thyroid cancer (DTC) in adults and children aged 12 years and older whose disease has progressed after vascular endothelial growth factor receptor targeted therapy and who are refractory to or ineligible for radioactive iodine (I-131) therapy. Guidelines indicate that for patients with metastatic radioactive iodine-refractory differentiated thyroid cancer, if disease progression is rapid, symptomatic, and/or urgent, and cannot be controlled by other methods, a tyrosine kinase inhibitor should be considered.
3. Renal Cell Carcinoma
Used as monotherapy for patients with advanced renal cell carcinoma (RCC); in combination with nivolumab as first-line treatment. Guidelines generally support the use of tyrosine kinase inhibitors, including cabozantinib, in treatment-naïve and treatment-experienced advanced renal cell carcinoma.
4. Hepatocellular Carcinoma
Used for patients with hepatocellular carcinoma (HCC) who have previously received sorafenib. Guidelines generally support the use of another tyrosine kinase inhibitor, including cabozantinib, as second-line treatment in HCC patients who have received multiple first-line therapies. The US FDA has designated it as an orphan drug for the treatment of hepatocellular carcinoma.
The above information is from the drug's official website and only reflects the indications for this drug in countries where it is registered overseas. It does not represent the approved use in mainland China. Please do not make any treatment decisions based on this information.
Cabozantinib Dosage and Administration
1. Differentiated Thyroid Cancer in Children
(1) Pediatric patients aged 12 years and older with a body surface area ≥ 1.2 m²:
60 mg daily. Continue treatment until disease progression or unacceptable toxicity occurs.
(2) Pediatric patients aged 12 years and older with a body surface area < 1.2 m²:
40 mg daily. Continue treatment until disease progression or unacceptable toxicity occurs.
2. Medullary Thyroid Carcinoma in Adults:
140 mg orally once daily (1 80 mg capsule and 3 20 mg capsules). Continue treatment until disease progression or unacceptable toxicity occurs.
3. Differentiated Thyroid Carcinoma
Adults with a body surface area ≥ 1.2 m²:
60 mg daily. Continue treatment until disease progression or unacceptable toxicity occurs.
4. Renal Cell Carcinoma
(1) Monotherapy: 60 mg daily. Continue treatment until disease progression or unacceptable toxicity occurs.
(2) In combination with nivolumab: 40 mg daily. In combination with nivolumab, 240 mg every 2 weeks (30-minute intravenous infusion) or 480 mg every 4 weeks (30-minute intravenous infusion). Continue treatment for up to 2 years, or until disease progression or unacceptable toxicity occurs.
5. Hepatocellular Carcinoma: 60 mg daily
Continue treatment until disease progression or unacceptable toxicity occurs.
The above information is from the drug's official website and only reflects the dosage and administration range of the drug in countries where it is registered outside of mainland China. It does not represent the approved use range in mainland China. Please do not make any treatment decisions based on this information.
Common Adverse Reactions of Cabozantinib:
1. Cabozantinib Capsules (Incidence ≥25%): Diarrhea, stomatitis, palmoplantar erythema sensory disturbance syndrome (hand-foot syndrome), weight loss, decreased appetite, nausea, fatigue, oral pain, hair color change, taste disturbance, hypertension, abdominal pain, constipation, elevated AST, elevated ALT, lymphopenia, elevated alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, hyperbilirubinemia.
2. Cabozantinib Tablets (Incidence ≥20%): Diarrhea, fatigue, palmoplantar erythema sensory disturbance syndrome (hand-foot syndrome), decreased appetite, hypertension, nausea, vomiting, weight loss, constipation.
3. Cabozantinib in combination with nivolumab (incidence ≥20%): Diarrhea, fatigue, hepatotoxicity, palmoplantar erythema sensory disturbance syndrome (hand-foot syndrome), stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, loss of appetite, nausea, taste disturbance, abdominal pain, cough, upper respiratory tract infection.
The above information is from the drug's official website and only reflects the range of side effects in countries where the drug is registered outside of mainland China. It does not represent the approved use range in mainland China. Please do not make any treatment decisions based on this information.
Recommended article: Adverse reactions of cabozantinib
Precautions for cabozantinib:
1. Perforation and fistula: Monitor patients for symptoms of perforation and fistula. Patients who develop gastrointestinal perforation or fistula should permanently discontinue cabozantinib.
2. Bleeding: Serious, sometimes fatal, bleeding, including hemoptysis and gastrointestinal bleeding, has been reported. This drug is contraindicated in patients with severe bleeding or a recent history of bleeding, hemoptysis, hematemesis, or melena. Treatment should be discontinued before surgery or if grade 3 or 4 bleeding occurs.
3. Thromboembolic Events: The risk of thromboembolic events is increased. There have been reports of venous thromboembolism and arterial thromboembolism. Cabozantinib should be permanently discontinued in patients experiencing acute myocardial infarction or arterial/venous thromboembolic events requiring medical intervention.
4. Impaired Wound Healing: Wound healing complications have been reported. Cabozantinib should be discontinued for at least 3 weeks before elective surgery (including invasive dental procedures). After major surgery, treatment can be resumed at least 2 weeks after clinical assessment of adequate wound healing. The safety of resuming cabozantinib after the resolution of wound healing complications has not been established.
5. Hypertension: The incidence of treatment-induced hypertension is increased. Cabozantinib should not be initiated in patients with uncontrolled hypertension. Blood pressure should be monitored regularly before and during treatment. For hypertension that is not adequately controlled with medication, cabozantinib should be discontinued; treatment should be resumed at a reduced dose once blood pressure is controlled. Cabozantinib should be permanently discontinued if a hypertensive crisis occurs or if hypertension remains uncontrolled despite best medical management.
6. Osteonecrosis of the jaw (ONJ) Osteonecrosis of the jaw has been reported. Symptoms may include jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or delayed healing of the oral cavity or jaw after dental surgery. Once the osteonecrosis of the jaw has resolved, cabozantinib tablets (Cabometyx) can be resumed at a reduced dose.
7. Diarrhea If diarrhea occurs, cabozantinib should be discontinued until the diarrhea resolves to grade 1, then resumed at a reduced dose.
8. Palmoplantar erythema sensory disturbance syndrome If palmoplantar erythema sensory disturbance syndrome occurs, temporary interruption of cabozantinib treatment and a reduced dose may be necessary.
9. Proteinuria Urinary protein should be monitored regularly during treatment. Cabozantinib should be permanently discontinued in patients who develop nephrotic syndrome. If proteinuria occurs, cabozantinib treatment may need to be temporarily interrupted and the dose reduced.
10. Reversible Posterior Encephalopathy Syndrome (RPLS) Reversible posterior encephalopathy syndrome should be considered when patients experience seizures, headache, visual disturbances, confusion, or altered mental function. Patients with reversible posterior encephalopathy syndrome should permanently discontinue cabozantinib.
11. Hepatotoxicity Compared to cabozantinib monotherapy, patients receiving cabozantinib tablets (Cabometyx) in combination with nivolumab have a higher incidence of grade 3 or 4 hepatotoxicity and elevated ALT/AST levels.
Depending on the severity, cabozantinib tablets (Cabometyx) should be discontinued, and the dose reduced upon resumption of treatment. Liver enzymes should be monitored regularly before and during treatment; more frequent monitoring should be considered when cabozantinib is used in combination with nivolumab. If liver enzymes are elevated, cabozantinib tablets (Cabometyx) and nivolumab treatment should be temporarily discontinued, and systemic corticosteroids should be considered.
12. Adrenal Insufficiency Primary or secondary adrenal insufficiency has been reported in patients receiving cabozantinib tablets (Cabometyx) in combination with nivolumab. In clinical trials, management of adrenal insufficiency has included the use of systemic corticosteroids, temporary discontinuation of the cabozantinib and nivolumab combination therapy, and/or hormone replacement therapy.
For grade 2 or higher adrenal insufficiency, symptomatic treatment (including hormone replacement therapy) should be initiated based on clinical indications. Depending on the severity, cabozantinib (Cabometyx) and/or nivolumab treatment should be temporarily suspended, and cabozantinib (Cabometyx) treatment should be resumed at a reduced dose.
12. Thyroid Dysfunction: Before initiating cabozantinib (Cabometyx), patients should be assessed for signs of thyroid dysfunction. During treatment, signs and symptoms of thyroid dysfunction should be monitored and managed according to clinical indications.
13. Hypocalcemia: Hypocalcemia has been reported in patients treated with cabozantinib. Monitor serum calcium levels and supplement with calcium if necessary. Depending on the severity, cabozantinib treatment may be discontinued after recovery from hypocalcemia and resumed at a reduced dose, or permanently discontinued.
14. Fetal/Neonatal Morbidity and Mortality: May cause harm to the fetus; has been shown to be embryotoxic, fetal toxic, and teratogenic in animals. Women of reproductive potential should be advised to use effective contraception during treatment with this drug and for 4 months after discontinuation. If this drug is used during pregnancy or if the patient becomes pregnant, they should be informed of the potential harm to the fetus.
Special Populations for Cabozantinib Use:
1. Pregnancy: May cause harm to the fetus. 1. Pregnancy Status: Before initiating treatment, confirm the pregnancy status of women of reproductive potential and advise them to use effective contraception during treatment with this drug and for 4 months after the last dose.
2. Breastfeeding: It is unclear whether cabozantinib or its metabolites enter human breast milk. The effects of this drug on breastfed infants or milk production are unknown. Women should not breastfeed during treatment and for 4 months after the last dose.
3. Women of Reproductive Potential and Men: Women of reproductive potential should be advised to use effective contraception during cabozantinib treatment and for 4 months after the last dose.
4. Pediatric Use: The safety and efficacy of cabozantinib tablets (Cabometyx) in differentiated thyroid carcinoma (DTC) in pediatric patients aged 12 years and older have been established; safety and efficacy in patients under 12 years of age have not been established. For children with open growth plates during treatment, monitoring of epiphyseal and longitudinal growth is recommended.
5. Use in the Elderly: Capsules: In patients aged 65 years and older, experience is limited, and it is impossible to determine whether the response differs from that in younger adults. In adults (20-86 years), pharmacokinetics were not affected by age.
Tablets: No overall difference in safety or efficacy was observed between patients aged 65 years and older and younger patients.
6. Hepatic Impairment: Mild to moderate hepatic impairment: Increased exposure to cabozantinib was observed.
Severe (Child-Pugh C) hepatic impairment: Not studied.
7. Renal Impairment: Not studied in patients with severe renal impairment or requiring dialysis. No dose adjustment of cabozantinib is required in patients with mild or moderate renal impairment.
Storage of Cabozantinib:
Capsules: 20-25°C (permissible deviation 15-30°C).
Tablets: 20-25°C (permissible deviation 15-30°C).
