Title:Cabozantinib in Thyroid Cancer
Volume: 10
Issue: 3
Author(s): Poupak Fallahi, Silvia M. Ferrari, Flavia Di Bari, Gabriele Materazzi, Salvatore Benvenga, Paolo Miccoli and Alessandro Antonelli
Affiliation:
Keywords:
Cabozantinib, differentiated thyroid carcinoma, epidermal growth factor receptor, medullary thyroid cancer, papillary
thyroid cancer, RET, tyrosine kinase inhibitors, vascular endothelial growth factor.
Abstract: Cabozantinib is an oral once-daily multitarget tyrosine kinase inhibitor of MET, VEGFR2,
RET, acting against KIT, AXL, FLT3 and Tie-2. Cabozantinib has shown anti-cancer effects in
preclinical and clinical models of cancers derived from both epithelial and mesenchymal origins [prostate
cancer, non small lung cancer, medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC), renal cell
carcinoma, etc.]. In a Phase III clinical study, cabozantinib improved PFS (11.2 months versus 4.0 months in the placebo
group) of patients with MTC (independently of age, bone metastases, RET status and prior treatment). Cabozantinib was
approved in 2012 by FDA for metastatic MTC and in 2013 by EMA. Cabozantinib has been also evaluated in metastatic
DTC patients, because they have activation on tyrosine kinases, including MET, VEGFR2 and RET, suggesting the possible
use of cabozantinib in metastatic DTC. Actually, two Phase II trials of cabozantinib in DTC patients resistant to RAI
are ongoing. To increase the antineoplastic effect of cabozantinib, and to overcome the occurence of drug resistance,
combination studies with other anticancer agents are ongoing. In conclusion, cabozantinib has shown to exert an important
therapeutic effect in patients with MTC improving PFS. In DTC patients, cabozantinib has shown promising results.