Cabozantinib for the Treatment of Advanced Medullary Thyroid Cancer
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Patients with advanced medullary thyroid cancer (MTC) have poor prognoses and limited treatment options. Improved knowledge about molecular aberrations associated with MTC and the availability of novel targeted tyrosine kinase inhibitors (TKIs) have led to new potential treatment modalities. Cabozantinib is an oral multitargeted TKI with activity against multiple receptors including RET, vascular endothelial growth factor receptor type 2 (VEGFR2), and MET that has been evaluated in MTC in the preclinical and clinical arenas.
This article reviews unmet clinical needs in advanced MTC. The authors consider novel agents that have been studied in MTC, with a focus on the investigational agent cabozantinib. Up-to-date clinical data of cabozantinib in MTC are discussed.
Recent clinical evaluation suggests that cabozantinib is the first agent to prolong progression-free survival in patients with progressive MTC. These findings indicate that cabozantinib may be an effective therapy in advanced MTC. No improvement in overall survival has been demonstrated but data are not mature.
Cabozantinib may be an effective treatment option for patients with advanced MTC and is worthy of further evaluation.
- Schlumberger, M., Carlomagno, F., Baudin, E., Bidart, J.M., Santoro, M. (2008) New therapeutic approaches to treat medullary thyroid carcinoma. Nat Clin Pract Endocrinol Metab 4: pp. 22-32 CrossRef
- Fugazzola, L., Muzza, M., Mian, C. (2008) RET genotypes in sporadic medullary thyroid cancer: studies in a large Italian series. Clin Endocrinol (Oxf) 69: pp. 418-425 CrossRef
- Mian, C., Pennelli, G., Barollo, S. (2011) Combined RET and Ki-67 assessment in sporadic medullary thyroid carcinoma: a useful tool for patient risk stratification. Eur J Endocrinol 164: pp. 971-976 CrossRef
- Elisei, R., Cosci, B., Romei, C. (2008) Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: A 10-year follow-up study. J Clin Endocrinol Metab 93: pp. 682-687 CrossRef
- Moura, M.M., Cavaco, B.M., Pinto, A.E., Leite, V. (2011) High prevalence of RAS mutations in RET-negative sporadic medullary thyroid carcinomas. J Clin Endocrinol Metab 96: pp. E863-E868 CrossRef
- Kurzrock, R., Sherman, S.I., Ball, D.W. (2011) Activity of XL184 (cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol 29: pp. 2660-2666 CrossRef
- Roman, S., Lin, R., Sosa, J.A. (2006) Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer 107: pp. 2134-2142 CrossRef
- Brierley, J., Sherman, E. (2012) The role of external beam radiation and targeted therapy in thyroid cancer. Semin Radiat Oncol 22: pp. 254-262 CrossRef
- Brierley, J., Tsang, R., Simpson, W.J., Gospodarowicz, M., Sutcliffe, S., Panzarella, T. (1996) Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control. Thyroid 6: pp. 305-310 CrossRef
- Fife, K.M., Bower, M., Harmer, C.L. (1996) Medullary thyroid cancer: The role of radiotherapy in local control. Eur J Surg Oncol 22: pp. 588-591 CrossRef
- Martinez, S.R., Beal, S.H., Chen, A., Chen, S.L., Schneider, P.D. (2010) Adjuvant external beam radiation for medullary thyroid carcinoma. J Surg Oncol 102: pp. 175-178 CrossRef
- Lessin, L.S. Medullary carcinoma of the thyroid; chemotherapy. In: Wartofsky, L., Nostrand, D. eds. (2006) Thyroid Cancer: A Comprehensive Guide to Clinical Management. Humana Press, Totowa, NJ, pp. 609-611
- Mahler, C., Verhelst, J., Longueville, M., Harris, A. (1990) Long-term treatment of metastatic medullary thyroid carcinoma with the somatostatin analogue octreotide. Clin Endocrinol (Oxf) 33: pp. 261-269 CrossRef
- Vitale, G., Tagliaferri, P., Caraglia, M. (2000) Slow release lanreotide in combination with interferon-alpha2b in the treatment of symptomatic advanced medullary thyroid carcinoma. J Clin Endocrinol Metab 85: pp. 983-988 CrossRef
- Frank-Raue, K., Fabel, M., Delorme, S., Haberkorn, U., Raue, F. (2007) Efficacy of imatinib mesylate in advanced medullary thyroid carcinoma. Eur J Endocrinol 157: pp. 215-220 CrossRef
- Groot, J.W., Zonnenberg, B.A., Ufford-Mannesse, P.Q. (2007) A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab 92: pp. 3466-3469 CrossRef
- Schlumberger, M.J., Elisei, R., Bastholt, L. (2009) Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol 27: pp. 3794-3801 CrossRef
- Lam, E.T., Ringel, M.D., Kloos, R.T. (2010) Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol 28: pp. 2323-2330 CrossRef
- De Souza JA, Busaidy N, Zimrin A, et al. Phase II trial of sunitinib in medullary thyroid cancer (MTC) [abstract]. J Clin Oncol. 2010;28(Suppl.). Abstract 5504.
- Cohen, E.E., Rosen, L.S., Vokes, E.E. (2008) Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 26: pp. 4708-4713 CrossRef
- Wells, S.A., Gosnell, J.E., Gagel, R.F. (2010) Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 28: pp. 767-772 CrossRef
- Wells, S.A., Robinson, B.G., Gagel, R.F. (2012) Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, doubleblind phase III trial. J Clin Oncol 30: pp. 134-141 CrossRef
- Robinson, B.G., Paz-Ares, L., Krebs, A., Vasselli, J., Haddad, R. (2010) Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Endocrinol Metab 95: pp. 2664-2671 CrossRef
- Schoffski P, Elisei R, Müller S, et al.; EXAM Study Group. An international, double-blind, randomized, placebo-controlled phase III trial (EXAM) of cabozantinib (XL184) in medullary thyroid carcinoma (MTC) patients (pts) with documented RECIST progression at baseline [abstract]. J Clin Oncol. 2012;30:(Suppl.). Abstract 5508.
- Groot, J.W., Zonnenberg, B.A., Plukker, J.T., Graaf, W.T., Links, T.P. (2005) Imatinib induces hypothyroidism in patients receiving levothyroxine. Clin Pharmacol Ther 78: pp. 433-438 CrossRef
- Wells SA, Gosnell JE, Gagel RF, et al. Vandetanib in metastatic hereditary medullary thyroid cancer: Follow-up results of an open-label phase II trial [abstract]. J Clin Oncol. 2007;25:(Suppl.). Abstract 6018.
- Vandetanib REMS Program. AstraZeneca Pharmaceuticals LP, 2001.
- Yakes, F.M., Chen, J., Tan, J. (2011) Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther 10: pp. 2298-2308 CrossRef
- Runeberg-Roos, P., Saarma, M. (2007) Neurotrophic factor receptor RET: structure, cell biology, and inherited diseases. Ann Med 39: pp. 572-580 CrossRef
- Capp, C., Wajner, S.M., Siqueira, D.R., Brasil, B.A., Meurer, L., Maia, A.L. (2010) Increased expression of vascular endothelial growth factor and its receptors, VEGFR-1 and VEGFR-2, in medullary thyroid carcinoma. Thyroid 20: pp. 863-871 CrossRef
- Bunone, G., Vigneri, P., Mariani, L. (1999) Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features. Am J Pathol 155: pp. 1967-1976 CrossRef
- Torre, N.G., Buley, I., Wass, J.A., Turner, H.E. (2006) Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour. Endocr Relat Cancer 13: pp. 931-944 CrossRef
- Joao Bugalho, M., Madureira, D., Espadinha, C., Paula Font, A., Sobrinho, L.G. (2008) Serum vascular endothelial growth factor levels in patients with medullary thyroid carcinoma. Eur J Endocrinol 159: pp. 167-169 CrossRef
- Feng, Y., Thiagarajan, P.S., Ma, P.C. (2012) MET signaling: novel targeted inhibition and its clinical development in lung cancer. J Thorac Oncol 7: pp. 459-467 CrossRef
- Papotti, M., Olivero, M., Volante, M. (2000) Expression of hepatocyte growth factor (HGF) and its receptor (MET) in medullary carcinoma of the thyroid. Endocr Pathol 11: pp. 19-30 CrossRef
- Joly, A.H. (2006) Simultaneous blockade of VEGF and HGF receptors results in potent anti-angiogenic and anti-tumor effects. Eur J Cancer Supplements 4: pp. 35 CrossRef
- Sennino, B., Ishiguro-Oonuma, T., Wei, Y. (2012) Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer Discov 2: pp. 270-287 CrossRef
- Cabozantinib for the Treatment of Advanced Medullary Thyroid Cancer
Advances in Therapy
Volume 29, Issue 11 , pp 925-934
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- Medullary thyroid cancer
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- Tyrosine kinase inhibitors
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