Keywords
proto-oncogene proteins B-raf
thyroid neoplasms
lenvatinib
sorafenib
protein kinase inhibitors
thyroid neoplasms
lenvatinib
sorafenib
protein kinase inhibitors
How to Cite
Román-González, A., Zapata, M. L., & Mejia, S. (2021). Tyrosine-kinase inhibitors for thyroid carcinoma. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 7(3), 170–176. https://doi.org/10.53853/encr.7.3.629
Abstract
ntroduction: Thyroid carcinoma is the most common endocrine neoplasia. An increase in the prevalence of this disease has been found and maybe related to over-diagnosis. However, an increase in larger tumor, aggressive variants and mortality has also been found. The cause of this change if currently unknown. Most patients with thyroid cancer have localized, low-risk disease. Between 1 to 5 % of thyroid carcinoma have metastasis. Half of them may have radioactive resistant tumor. Therapeutical options in these patients has been limited.
Methods: A literature review of randomized clinical trials versus placebo evaluating tyrosine-kinase inhibitors in thyroid carcinoma was performed. A synthesis of the results is presents was well as general indications for metastatic disease management.
Results: To the date of publication of this article, the only approved drug in Colombia to treat advanced thyroid carcinoma is sorafenib. In other countries, Lenvatinib has been approved. The combination of dabrafenib plus trametinib was recently approved by the FDA to be used in patients with BRAF mutations. An active management of side effects is required for a successful and safe treatment.
Conclusions: Radioactive resistant thyroid carcinoma is a clinical challenge. Tyrosine-kinase inhibitors are an option for these patients. Side effects management is essential for an appropriate and successful use.
References
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2. Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016;388(10061):2783-95. doi: 10.1016/S0140-6736(16)30172-6
3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394- 424. doi: 10.3322/caac.21492
4. Galofré JC, Santamaría-Sandi J, Capdevila J, Navarro-González E, ZafónLlopis C, Ramón Y Cajal Asensio T, et al. Consensus on the management of advanced medullary thyroid carcinoma on behalf of the Working Group of Thyroid Cancer of the Spanish Society of Endocrinology (SEEN) and the Spanish Task Force Group for Orphan and Infrequent Tumors (GETHI). Endocrinol Nutr. 2015;62(4):e37-46. doi: 10.1016/j.endonu.2015.01.005
5. Spitzweg C, Morris JC, Bible KC. New drugs for medullary thyroid cancer: new promises? Endocr Relat Cancer. 2016;23(6):R287-97. doi: 10.1530/ ERC-16-0104
6. Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384(9940):319-28. doi: 10.1016/S0140-6736(14)60421-9
7. Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372(7):621-30. doi: 10.1056/NEJMoa1406470
8. Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A, et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2012;13(9):897-905. doi: 10.1016/S1470-2045(12)70335-2
9. Thornton K, Kim G, Maher VE, Chattopadhyay S, Tang S, Moon YJ, et al. Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary. Clin Cancer Res. 2012;18(14):3722-30. doi: 10.1158/1078-0432.CCR-12- 0411
10. Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30(2):134-41. doi: 10.1200/JCO.2011.35.5040
11. Hoy SM. Cabozantinib: a review of its use in patients with medullary thyroid cancer. Drugs. 2014;74(12):1435-44. doi: 10.1007/s40265-014- 0265-x
12. Haroon Al Rasheed MR, Xu B. Molecular Alterations in Thyroid Carcinoma. Surg Pathol Clin. 2019;12(4):921-30. doi: 10.1016/j.path.2019.08.002
13. Brose MS, Cabanillas ME, Cohen EE, Wirth LJ, Riehl T, Yue H, et al. Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17(9):1272-82. doi: 10.1016/S1470-2045(16)30166-8
14. Jhiang SM. The RET proto-oncogene in human cancers. Oncogene. 2000;19(49):5590-7. doi: 10.1038/sj.onc.1203857
15. Takahashi M, Ritz J, Cooper GM. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985;42(2):581-8. doi: 10.1016/0092-8674(85)90115-1
16. Drilon A, Hu ZI, Lai GGY, Tan DSW. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol. 2018;15(3):151-67. doi: 10.1038/nrclinonc.2017.175
17. Ji JH, Oh YL, Hong M, Yun JW, Lee HW, Kim D, et al. Identification of Driving ALK Fusion Genes and Genomic Landscape of Medullary Thyroid Cancer. PLoS Genet. 2015;11(8):e1005467. doi: 10.1371/journal.pgen.1005467
18. Bagheri-Yarmand R, Williams MD, Grubbs EG, Gagel RF. ATF4 Targets RET for Degradation and Is a Candidate Tumor Suppressor Gene in Medullary Thyroid Cancer. J Clin Endocrinol Metab. 2017;102(3):933-41. doi: 10.1210/jc.2016-2878
19. Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567-610. doi: 10.1089/ thy.2014.0335
20. Barroso-Sousa R, Lerario AM, Evangelista J, Papadia C, Lourenço DM, Lin CS, et al. Complete resolution of hypercortisolism with sorafenib in a patient with advanced medullary thyroid carcinoma and ectopic ACTH (adrenocorticotropic hormone) syndrome. Thyroid. 2014;24(6):1062-6. doi: 10.1089/thy.2013.0571
21. Baudry C, Paepegaey AC, Groussin L. Reversal of Cushing’s syndrome by vandetanib in medullary thyroid carcinoma. N Engl J Med. 2013;369(6):584-6. doi: 10.1056/NEJMc1301428
22. Hadoux J, Pacini F, Tuttle RM, Schlumberger M. Management of advanced medullary thyroid cancer. Lancet Diabetes Endocrinol. 2016;4(1):64-71. doi: 10.1016/S2213-8587(15)00337-X
23. Dadu R, Hu MN, Grubbs EG, Gagel RF. Use of Tyrosine Kinase Inhibitors for Treatment of Medullary Thyroid Carcinoma. Recent Results Cancer Res. 2015;204:227-49. doi: 10.1007/978-3-319-22542-5_11
24. Frampton JE. Vandetanib: in medullary thyroid cancer. Drugs. 2012;72(10):1423-36. doi: 10.2165/11209300-000000000-00000
25. Gómez K, Varghese J, Jiménez C. Medullary thyroid carcinoma: molecular signaling pathways and emerging therapies. J Thyroid Res. 2011;2011:815826. doi: 10.4061/2011/815826
26. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10(12):2298- 308. doi: 10.1158/1535-7163.MCT-11-0264
27. Gordon MS, Vogelzang NJ, Schoffski P, Daud A, Spira AI, O’Keeffe BA, et al. Activity of cabozantinib (XL184) in soft tissue and bone: Results of a phase II randomized discontinuation trial (RDT) in patients (pts) with advanced solid tumors. J Clin Oncol. 2011;29 (Suppl 15)3010-3010. doi: 10.1200/ jco.2011.29.15_suppl.3010
28. Al-Salama ZT, Keating GM. Cabozantinib: A Review in Advanced Renal Cell Carcinoma. Drugs. 2016;76(18):1771-8. doi: 10.1007/s40265-016-0661-5
29. Jimenez C, Waguespack S, Habra M, Busaidy N, Dadu R, Tamsen G, et al. Cabozantanib in patients with unresectable metastatic pheochromocytoma and paraganglioma. Global Academic Programs of Cancer Centers Symposium; Houston, Tx2017.
30. Roman-Gonzalez A, Jimenez C. Malignant pheochromocytoma-paraganglioma: pathogenesis, TNM staging, and current clinical trials. Curr Opin Endocrinol Diabetes Obes. 2017;24(3):174-183. doi: 10.1097/ MED.0000000000000330
31. Cohen EE, Tortorici M, Kim S, Ingrosso A, Pithavala YK, Bycott P. A Phase II trial of axitinib in patients with various histologic subtypes of advanced thyroid cancer: long-term outcomes and pharmacokinetic/pharmacodynamic analyses. Cancer Chemother Pharmacol. 2014;74(6):1261-70. doi: 10.1007/s00280-014-2604-8
32. Frank-Raue K, Ganten M, Kreissl MC, Raue F. Rapid response to sorafenib in metastatic medullary thyroid carcinoma. Exp Clin Endocrinol Diabetes. 2011;119(3):151-5. doi: 10.1055/s-0030-1262836
33. Ravaud A, de la Fouchardière C, Asselineau J, Delord JP, Do Cao C, Niccoli P, et al. Efficacy of sunitinib in advanced medullary thyroid carcinoma: intermediate results of phase II THYSU. Oncologist. 2010;15(2):212-3; author reply 4. doi: 10.1634/theoncologist.2009-0303
34. van Geel RM, Beijnen JH, Schellens JH. Concise drug review: pazopanib and axitinib. Oncologist. 2012;17(8):1081-9. doi: 10.1634/theoncologist.2012-0055
35. Bass MB, Sherman SI, Schlumberger MJ, Davis MT, Kivman L, Khoo HM, et al. Biomarkers as predictors of response to treatment with motesanib in patients with progressive advanced thyroid cancer. J Clin Endocrinol Metab. 2010;95(11):5018-27. doi: 10.1210/jc.2010-0947
36. Sherman SI, Wirth LJ, Droz JP, Hofmann M, Bastholt L, Martins RG, et al. Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med. 2008;359(1):31-42. doi: 10.1056/NEJMoa075853
37. Kummar S, Lassen UN. TRK Inhibition: A New Tumor-Agnostic Treatment Strategy. Target Oncol. 2018;13(5):545-56. doi: 10.1007/s11523-018- 0590-1
38. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15(12):731-47. doi: 10.1038/ s41571-018-0113-0
39. Scott LJ. Larotrectinib: First Global Approval. Drugs. 2019;79(2):201-6. doi: 10.1007/s40265-018-1044-x
40. Laetsch TW, Hawkins DS. Larotrectinib for the treatment of TRK fusion solid tumors. Expert Rev Anticancer Ther. 2019;19(1):1-10. doi: 10.1080/14737140.2019.1538796
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