Cabozantinib (Efficacy)

Cabozantinib is a tyrosine kinase inhibitor used for the treatment of medullary thyroid cancer. Patients with the M918T mutation of the RET gene respond better to treatment with cabozantinib.

Cabozantinib is a small molecule that inhibits several tyrosine kinase receptors involved in tumor growth and angiogenesis, pathologic bone remodeling and metastatic cancer progression. Cabozantinib is used in the treatment of patients with progressive metastatic medullary thyroid cancer.

Medullary thyroid cancer (MTC) is a form of thyroid carcinoma which originates parafollicular cells of the thyroid gland (C cells), which produce the hormone called calcitonine. Medullary tumors are the third most common of all thyroid cancers; they are about 3% of all thyroid cancer cases.

Biochemical markers currently used for the diagnosis and monitoring of the disease are serum concentration of calcitonine and carcinoembryonic antigen.

To the date, surgery and radiation therapy have been the major treatments for medullary thyroid carcinoma, but today oncologists consider the treatment with TKIs (tyrosin-kinase inhibitors) as cabozantinib.

One of the prognosis markers for the response to cabozantinib in patients with MTC is the presence of the M918T RET mutation (RET+ patients). RET is a tyrosine kinase receptor which mutation is involved in pathologic processes such as oncogenesis, metastasis, angiogenesis, and maintenance of the tumor microenvironment.

Cabozantinib is administered orally and the recommended daily dose of 140 mg (divided in one 80 mg shot and three 20 mg capsules).

The treatment is continued until the progression of the disease occurs or if there is a risk due to the toxicity of the drug.



Genes analyzed



Sherman SI, Clary DO, Elisei R, Schlumberger MJ, Cohen EEW, Schöffski P, et al. Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer. Cancer, 2016; 122(24):3856–64.

Romei C, Tacito A, Molinaro E, et al. Twenty years of lesson learning: how does the RET genetic screening test impact the clinical management of medullary thyroid cancer?. Clin. Endocrinol (Oxf.), 2015, 82 (6):892-9.

Elisei R, Schlumberger MJ, Müller SP, Schöffski P, Brose MS, Shah MH, et al. Cabozantinib in Progressive Medullary Thyroid Cancer. J Clin Oncol, 2013 Oct 10; 31(29):3639–46.

Ruiz-Garcia E, Vidal-Millan S, Lopez-Yañez A, et al. Search of the p.M918T Mutation in the RET Oncogene in Mexican Adult Patients with Medullary Thyroid Carcinoma. Exp.. Clin. Endocrinol. Diabetes, 2017; 125 (4): 218-222.

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