Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Advanced Thyroid Cancer

Author(s): Emanuela Vaccher, Ornella Schioppa, Ferdinando Martellotta, Giulia Fornasier, Elisa Giacomin, Francesco Lo Re, Paolo Baldo*, Giuseppe Corona, Carlo Gobitti.

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 14 , Issue 3 , 2019

Become EABM
Become Reviewer

Abstract:

Background: Thyroid cancer is the most common endocrine neoplasia and represents approximately 1.5% to 2.1% of all cancers diagnosed annually worldwide. Iodine Refractory Differentiated Thyroid Carcinoma (RR-DTC) and advanced/metastatic medullary thyroid carcinoma are relatively uncommon yet prognostically significant thyroid cancers. Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers, including thyroid cancer. Many Multi-Kinase Inhibitors (MKIs) which are now FDA-/EMA approved for thyroid cancer have shown clinical benefit in patients with advanced cancer. Treatment related toxicities occur frequently with these drugs and can be severe or life-threatening.

Objectives: This review summarizes the role of targeted therapy with MKIs in the management of RRDTC and advanced/metastatic MTC patients, focusing on side-effect profiles of these drugs, with a presentation of several recent patents published in this field.

Methods: We review the scientific literature on advanced thyroid cancer and analyze the International Pharmacovigilance database (FAERS, Eudravigilance, and WHO Vigibase) for adverse drug reactions.

Results: This systematic analysis highlights the difference in the safety profile of the recent drugs used in the treatment of advanced thyroid cancer and the recent discoveries for diagnosis or treatment of the thyroid cancer.

Conclusion: It is essential to investigate the safety profile of recent anticancer drugs for advanced thyroid cancer to allow health professionals to make the best choice for each patient by conducting risk/benefit assessment.

Keywords: Advanced medullary thyroid carcinoma, adverse events, iodine-refractory thyroid cancer, multi-kinase inhibitors, toxicity profile.

[1]
Maniakas A, Davies L, Zafereo ME. Thyroid disease around the World. Otolaryngol Clin North Am 2018; 51(3): 631-42.
[2]
Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. JAMA 2017; 317(13): 1338-48.
[3]
Wells SA, Pacini F, Robinson BG, Santoro M. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: An update. J Clin Endocrinol Metab 2013; 98(8): 3149-64.
[4]
Nguyen QT, Lee EJ, Huang MG, Park YI, Khullar A, Plodkowski RA. Diagnosis and treatment of patients with thyroid cancer. Am Health Drug Benefits 2015; 8(1): 30-40.
[5]
Davicioni E, Haddad Z. Thyroid cancer diagnostics. US9994907 . (2018).
[6]
Hahn MA, Yim JH, Fong Y, Li XA, Wu X. Methods, treatment, and compositions for characterizing thyroid nodule . US15217645 . 2017.
[7]
Wei W-J, Shen C-T, Song H-J, Qiu Z-L, Luo Q-Y. MicroRNAs as a potential tool in the differential diagnosis of thyroid cancer: A systematic review and meta-analysis. Clin Endocrinol (Oxf) 2016; 84(1): 127-33.
[8]
De la Chapelle A, Eisfeild AK. Methods and compositions using MIR-3151 in the diagnosis and treatment of thyroid cancer. US9708612. (2017).
[9]
Keller A, Meese E, Borries A, Staehler F, Beier M. miRNA fingerprint in the diagnosis of diseases. US9702008 . (2017).
[10]
Yanai GL, Meiri E, Spector Y, Benjamin H, Dromi N. miRNA expression signature in the classification of thyroid tumors. US9708667 . (2017).
[11]
Fagin JA, Mitsiades N. Molecular pathology of thyroid cancer: Diagnostic and clinical implications. Best Pract Res Clin Endocrinol Metab 2008; 22(6): 955-69.
[12]
Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest 2016; 126(3): 1052-66.
[13]
Shibuya M. Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis. BMB Rep 2008; 41(4): 278-86.
[14]
Soares P, Trovisco V, Rocha AS, Lima J, Castro P, Preto A, et al. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene 2003; 22(29): 4578-80.
[15]
Yoo S-K, Lee S, Kim S-J, Jee H-G, Kim B-A, Cho H, et al. Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers. PLoS Genet 2016; 12(8)e1006239
[16]
Zaballos MA, Santisteban P. Key signaling pathways in thyroid cancer. J Endocrinol 2017; 235(2): R43-61.
[17]
Elisei R, Romei C, Vorontsova T, Cosci B, Veremeychik V, Kuchinskaya E, et al. RET/PTC rearrangements in thyroid nodules: Studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults. J Clin Endocrinol Metab 2001; 86(7): 3211-6.
[18]
Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: Benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 2006; 91(8): 2892-9.
[19]
Jin Y, Van Nostrand D, Cheng L, Liu M, Chen L. Radioiodine refractory differentiated thyroid cancer. Crit Rev Oncol Hematol 2018; 125: 111-20.
[20]
Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: Demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer 2006; 107(9): 2134-42.
[21]
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 Off J Am Soc Clin Oncol 2012; 30(2): 134-41.
[22]
Elisei R, Schlumberger MJ, Müller SP, Schöffski P, Brose MS, Shah MH, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol 2013; 31(29): 3639-46.
[23]
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 Lond Engl 2014; 384(9940): 319-28.
[24]
Worden F. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol 2014; 6(6): 267-79.
[25]
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.
[26]
Cabanillas ME, Habra MA. Lenvatinib: Role in thyroid cancer and other solid tumors. Cancer Treat Rev 2016; 42: 47-55.
[27]
De Falco V, Carlomagno F, Li H-Y, Santoro M. The molecular basis for RET tyrosine-kinase inhibitors in thyroid cancer. Best Pract Res Clin Endocrinol Metab 2017; 31(3): 307-18.
[28]
Matrone A, Valerio L, Pieruzzi L, Giani C, Cappagli V, Lorusso L, et al. Protein kinase inhibitors for the treatment of advanced and progressive radiorefractory thyroid tumors: From the clinical trials to the real life. Best Pract Res Clin Endocrinol Metab 2017; 31(3): 319-34.
[29]
Lange AM, Lo H-W. Inhibiting TRK proteins in clinical cancer therapy. Cancers 2018; 10(4)E105
[30]
Stull RA, Saunders L, Dylla S, et al. Anti-DLL3 antibody drug conjugates and methods of use. US9937268 . (2018).
[31]
Stull RA, Saunders L, Dylla SJ, et al. Methods of delivering DLL3 antibody drug conjugates. US9878053 . (2018).
[32]
Miliotou AN, Papadopoulou LC. CAR T-cell therapy: A new era in cancer immunotherapy. Curr Pharm Biotechnol 2018; 19(1): 5-18.
[33]
Xiao L, Wu Z, Pu C, Cao Z, Sun H, Bi M. Use of chimeric antigen receptor modified cells to treat cancer. US9932405 . (2018).
[34]
Spee PJL, Padkaer SB. Anti-NKG2A antibodies and uses thereof. US9683041 . (2017).
[35]
Chave G, Dayde-Cazals B, Fauvel B, Bories C, Yasri A. Azaindole derivates as multi kinase inhibitors. US9550772 . (2017).
[36]
Pacini F. Which patient with thyroid cancer deserves systemic therapy and when? Best Pract Res Clin Endocrinol Metab 2017; 31(3): 291-4.
[37]
Brose MS, Worden FP, Newbold KL, Guo M, Hurria A. Effect of age on the efficacy and safety of lenvatinib in radioiodine-refractory differentiated thyroid cancer in the Phase III SELECT trial. J Clin Oncol 2017; 35(23): 2692-9.
[38]
Funahashi Y, Kadowaki T, Matsui J, Simon JS, Xu L. Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compound. US9945862 . (2018).
[39]
Liu J-W, Chen C, Loh E-W, Chu C-C, Wang M-Y, Ouyang H-J, et al. Tyrosine kinase inhibitors for advanced or metastatic thyroid cancer: a meta-analysis of randomized controlled trials. Curr Med Res Opin 2018; 34(5): 795-803.
[40]
Brose MS, Bible KC, Chow LQM, Gilbert J, Grande C, Worden F, et al. Management of treatment-related toxicities in advanced medullary thyroid cancer. Cancer Treat Rev 2018; 66: 64-73.
[41]
Santoni M, Guerra F, Conti A, Lucarelli A, Rinaldi S, Belvederesi L, et al. Incidence and risk of cardiotoxicity in cancer patients treated with targeted therapies. Cancer Treat Rev 2017; 59: 123-31.
[42]
Zang J, Wu S, Tang L, Xu X, Bai J, Ding C, et al. Incidence and risk of QTc interval prolongation among cancer patients treated with vandetanib: A systematic review and meta-analysis. PLoS One 2012; 7(2) e30353
[43]
Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med 2016; 375(15): 1457-67.
[44]
Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 2009; 9(1): 28-39.
[45]
Widmer N, Bardin C, Chatelut E, Paci A, Beijnen J, Levêque D, et al. Review of therapeutic drug monitoring of anticancer drugs part two--targeted therapies. Eur J Cancer Oxf Engl 2014; 50(12): 2020-36.
[46]
Agrawal VR, Jodon G, Mushtaq R, Bowles DW. Update on multikinase inhibitor therapy for differentiated thyroid cancer. Drugs Today 2018; 54(9): 535-45.
[47]
EMA. Kisplyx, INN-lenvatinib - European Medicines Agency - europa.eu. Available at:. http: //www.ema.europa.eu/docs/en_GB/ document_library/EPAR_-_Product_Information/human/004224/ WC500216237.pdf (Accessed on: June 28, 2019)
[48]
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.
[49]
Fallahi P, Ferrari SM, Di Bari F, Materazzi G, Benvenga S, Miccoli P, et al. Cabozantinib in thyroid cancer. Recent Patents Anticancer Drug Discov 2015; 10(3): 259-69.
[50]
EMA. Cabometyx, INN-Cabozantinib - europa.eu. Available at:. www.ema.europa.eu/docs/it_IT/document_library/EPAR.../WC500214071.pdf (Accessed on June 28, 2019)
[51]
Weitzman SP, Cabanillas ME. The treatment landscape in thyroid cancer: A focus on cabozantinib. Cancer Manag Res 2015; 7: 265-78.
[52]
Cooper MR, Yi SY, Alghamdi W, Shaheen DJ, Steinberg M. Vandetanib for the treatment of medullary thyroid carcinoma. Ann Pharmacother 2014; 48(3): 387-94.
[53]
Fallahi P, Di Bari F, Ferrari SM, Spisni R, Materazzi G, Miccoli P, et al. Selective use of vandetanib in the treatment of thyroid cancer. Drug Des Devel Ther 2015; 9: 3459-70.
[54]
Johansson S, Read J, Oliver S, Steinberg M, Li Y, Lisbon E, et al. Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine. Clin Pharmacokinet 2014; 53(9): 837-47.
[55]
Martin P, Oliver S, Robertson J, Kennedy S-J, Read J, Duvauchelle T. Pharmacokinetic drug interactions with vandetanib during coadministration with rifampicin or itraconazole. Drugs R D 2011; 11(1): 37-51.
[56]
Hong DS, Kurzrock R, Wheler JJ, Naing A, Falchook GS, Fu S, et al. Phase I dose-escalation study of the multikinase inhibitor lenvatinib in patients with advanced solid tumors and in an expanded cohort of patients with melanoma. Clin Cancer Res Off J Am Assoc Cancer Res 2015; 21(21): 4801-10.
[57]
Krajewska J, Kukulska A, Jarzab B. Drug safety evaluation of lenvatinib for thyroid cancer. Expert Opin Drug Saf 2015; 14(12): 1935-43.
[58]
Zhu C, Ma X, Hu Y, Guo L, Chen B, Shen K, et al. Safety and efficacy profile of lenvatinib in cancer therapy: A systematic review and meta-analysis. Oncotarget 2016; 7(28): 44545-57.
[59]
VigiAccess. Available at:. http: //www.vigiaccess.org/ (Accessed on: June 28, 2019)
[60]
Cabanillas ME, Brose MS, Holland J, Ferguson KC, Sherman SI. A Phase I study of cabozantinib (XL184) in patients with differentiated thyroid cancer. Thyroid Off J Am Thyroid Assoc 2014; 24(10): 1508-14.
[61]
Schlumberger M, Elisei R, Müller S, Schöffski P, Brose M, Shah M, et al. Overall survival analysis of EXAM, a Phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma. Ann Oncol Off J Eur Soc Med Oncol 2017; 28(11): 2813-9.
[62]
Tsang VHM, Robinson BG, Learoyd DL. The safety of vandetanib for the treatment of thyroid cancer. Expert Opin Drug Saf 2016; 15(8): 1107-13.
[63]
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.
[64]
Sidaway P. Thyroid cancer: Cabozantinib effective in selected patients. Nat Rev Clin Oncol 2017; 14(12): 712.
[65]
EMA. Caprelsa, INN vandetanib - europa.eu. Available at:. https://www.ema.europa.eu/en/documents/product-information/caprelsa-epar-product-information_en.pdf (Accessed on June 28, 2019)


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 14
ISSUE: 3
Year: 2019
Page: [226 - 241]
Pages: 16
DOI: 10.2174/1574892814666190726143011
Price: $58

Article Metrics

PDF: 35
HTML: 4

Special-new-year-discount