A potent dual inhibitor of the MET (mesenchymal-epithelial transition factor) and VEGF and RET pathways designed to block MET driven tumor escape.

In multiple preclinical studies cabozantinib has been shown to kill tumor cells, reduce metastases, and inhibit angiogenesis.

Cabozantinib (COMETRIQ), for the treatment of patients with progressive metastatic medullary thyroid cancer (MTC).

Findings from the phase 3 COSMIC-311 trial led to the approval of cabozantinib in patients with radioactive iodine–refractory locally advanced or metastatic differentiated thyroid cancer.


Approved for adult and pediatric patients aged 12 years or older with locally advanced or metastatic differentiated thyroid cancer (DTC) who have experienced progression following treatment with VEGFR targeted therapy and whose disease is refractory to radioactive iodine.


Investigators reported a median progression-free survival of 11.0 months in the cabozantinib arm compared with 1.9 months in the placebo arm.

A small molecule that inhibits the activity of multiple tyrosine kinases, including RET, MET, AXL and VEGF receptor 2.

Tagets MET, VEGFR2, RET, AXL, and KIT, TAM protein kinases involved in development and progression of many cancers.

Inhibits c-MET

MET and AXL are involved with resistance development to VEGFR targeting therapy.

Decreases the regulatory T cells in the micro environment

A phase 3 study has met the requirements progression free survival in patients with progressive, unresectable, locally, or metastatic performance of medullary thyroid cancer.

Has efficacy in multiple tumor types: renal cell carcinoma, medullary thyroid cancer, hepatocellular cancer, differentiated thyroid cancer and prostate cancer.

EXAM trial 330 patients with medullary thyroid cancer showed a medium PFS of 6.7 months versus 3.4 months with placebo.

In a study of 330 patients, a statistically significant PFS prolongation was demonstrated in the cabozantinib arm compared to the placebo arm with an estimated median PFS of 11.2 months compared to 4.0 months for the placebo arm.

The overall response rate was 27%, but all were partial responses, and the median response duration was 14.7 months.

Approved for the treatment of advanced renal carcinoma in untreated patients and those previously treated with anti-angiogenic therapy.

In the phase 3 METEOR trial the drug was compared with Everiolimus in advanced or metastatic renal cell cancer: Progression free survival was significantly improved, with a 42% reduction in the risk of progression or death-7.4 months versus 3.8 months and median overall survival 21.4 months versus 16.5 months.

It significantly prolongs progression free survival in  patients with radioiodine refractory differentiated thyroid cancer.

Adverse reactions observed in 25% of cabozantinib-treated patients: were diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), weight loss, anorexia, nausea, fatigue, oral pain, hypopigmentation/graying of the hair, dysgeusia, hypertension, abdominal pain, and constipation.

Lab abnormalities in 25% were increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

Grade 3-4 adverse reactions occurs in 5% of patients included diarrhea, PPES, lymphopenia, hypocalcemia, fatigue, hypertension, asthenia, increased ALT, decreased weight, stomatitis, and decreased appetite.

The most common adverse effects (AEs) reported in 25% of patients were diarrhea, palmar-plantar erythrodysesthesia, fatigue, hypertension, and stomatitis. 



Additionally, common grade 3/4 AEs included palmar-plantar erythrodysesthesia, hypertension, fatigue, diarrhea, and stomatitis. 



34% of patients treated with cabozantinib experienced serious adverse effects:  diarrhea, pleural effusion, pulmonary embolism, and dyspnea. 



Fatal AEs such as arterial hemorrhage (0.8%) and pulmonary embolism (0.8%) affected 1.6% of those in the cabozantinib arm. 

Serious adverse reactions attributed to cabozantinib include:osteonecrosis of the jaw, reversible posterior leukoencephalopathy syndrome, pancreatitis, nephrotic syndrome, major hemorrhage, and perforation/fistula.

The recommended dose and schedule for cabozantinib is 140 mg orally once daily.

Patients should not eat for at least 2 hours before and 1 hour after taking the drug.

Dose reduction is required in 79% of patients.

Has efficacy for advanced prostate cancer, ovarian cancer, liver cancer and melanoma lesions.

In a randomized trial of 658 patients with RCC who received cabozantinib at dose is 60 mg a day or everolimus at a dose of 10 mg a day: the medium progression free survival was 7.4 months for cabozantinib and was 3.8 months for everolimus (Choueiri TK et al).

Cabozantinib sup[erior to sunitinib in advanced renal cell carcinoma with a median PFS of 8.6 months vs 5.3 months for sunitinib.

Cabometyx is a kinase inhibitor indicated for the treatment of patients with advanced renal cancer who have had previous anti-angiogenesis therapy.

Is a tablet unlike cabozantinub capsules.

Dosage of Cabometyx 60 mg daily.

Cabometyx should not be administered with a recent history of severe hemorrhage,

should be discontinued with gastrointestinal fistulas, G.I. perforations,

should be discontinued for myocardial infarction,, cerebral infarction, other serious arterial thrombolic events, and hypertensive crisis,.

Cabometyx may be associated with severe diarrhea, palmar-plantar erythrodysesthesia syndrome.

Cabometyx may be associated with reversible posterior leukoencephalopathy syndrome.

In hepatoma, among patients who have failed 1 therapy, median overall survival was 15.1 months and median progression free survival 4.4 months 5% achieving a partial remission, 78% of patients stable disease since that percent with progressive disease.

May have significant efficacy in neuroendocrine tumors.

May have activity in heavily pre-treated, platinum refractory patients with metastatic urothelial cancer.

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