Emerging Therapies for Progressive Metastatic Medullary Thyroid Cancer

  • Jessica E. Zwiener
  • Lily J. Kwatampora
  • Naifa L. Busaidy
Chapter
First Online:

Abstract

Targeted therapy in progressive metastatic medullary thyroid cancer (MTC) with current FDA-approved agents, vandetanib and cabozantinib, is associated with improved progression-free survival.

Keywords

Thyroid Cancer Idiopathic Pulmonary Fibrosis Vascular Endothelial Growth Factor Receptor Medullary Thyroid Cancer Anaplastic Thyroid Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Elisei R, Schlumberger MJ, Muller SP, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013;31:3639–46.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Wells SA Jr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30:134–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Orlandi F, Caraci P, Berruti A, et al. Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer. Ann Oncol. 1994;5:763–5.PubMedGoogle Scholar
  4. 4.
    Food and Drug Administration. CDER clinical pharmacology and biopharmaceutics review[s] for cabozantinib [COMETRIQ], 2012.Google Scholar
  5. 5.
    Carlomagno F, Guida T, Anaganti S, et al. Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors. Oncogene. 2004;23:6056–63.CrossRefPubMedGoogle Scholar
  6. 6.
    Mologni L, Redaelli S, Morandi A, et al. Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase. Mol Cell Endocrinol. 2013;377:1–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Cote GJ, Grubbs E, Hofmann MC. Thyroid C-cell biology and oncogenic transformation. In: Raue F, editor. Medullary thyroid carcinoma: Biology—Management—Treatment. Springer International Publishing; 2015 (in press).Google Scholar
  8. 8.
    Mian C, Pennelli G, Barollo S, et al. Combined RET and Ki-67 assessment in sporadic medullary thyroid carcinoma: a useful tool for patient risk stratification. Eur J Endocrinol. 2011;164:971–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Elisei R, Cosci B, Romei C, et al. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab. 2008;93:682–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Moura MM, Cavaco BM, Leite V. RAS proto-oncogene in medullary thyroid carcinoma. Endocr Relat Cancer. 2015;22:R235–52.CrossRefPubMedGoogle Scholar
  11. 11.
    Hong DS, Cabanillas ME, Wheler J, et al. Inhibition of the Ras/Raf/MEK/ERK and RET kinase pathways with the combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in medullary and differentiated thyroid malignancies. J Clin Endocrinol Metab. 2011;96:997–1005.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Rapa I, Saggiorato E, Giachino D, et al. Mammalian target of rapamycin pathway activation is associated to RET mutation status in medullary thyroid carcinoma. J Clin Endocrinol Metab. 2011;96:2146–53.CrossRefPubMedGoogle Scholar
  13. 13.
    Lyra J, Vinagre J, Batista R, et al. mTOR activation in medullary thyroid carcinoma with RAS mutation. Eur J Endocrinol. 2014;171:633–40.CrossRefPubMedGoogle Scholar
  14. 14.
    Tamburrino A, Molinolo AA, Salerno P, et al. Activation of the mTOR pathway in primary medullary thyroid carcinoma and lymph node metastases. Clin Cancer Res. 2012;18:3532–40.CrossRefPubMedGoogle Scholar
  15. 15.
    Manfredi GI, Dicitore A, Gaudenzi G, et al. PI3K/Akt/mTOR signaling in medullary thyroid cancer: a promising molecular target for cancer therapy. Endocrine. 2015;48:363–70.CrossRefPubMedGoogle Scholar
  16. 16.
    Sherman E, Ho A, Fury M, et al. Combination of everolimus and sorafenib in the treatment of thyroid cancer: update on phase II study. J Clin Oncol. 2015;33.Google Scholar
  17. 17.
    van Veelen W, Klompmaker R, Gloerich M, et al. P18 is a tumor suppressor gene involved in human medullary thyroid carcinoma and pheochromocytoma development. Int J Cancer. 2009;124:339–45.CrossRefPubMedGoogle Scholar
  18. 18.
    Bagheri-Yarmand R, Sinha KM, Gururaj AE, et al. A novel dual kinase function of the RET proto-oncogene negatively regulates activating transcription factor 4-mediated apoptosis. J Biol Chem. 2015;290:11749–61.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Dadu R, Rodriguez J, Wistuba I, et al. Immune markers in medullary thyroid cancer (MTC) and their clinical significance. Paper presented at the International Thyroid Congress, Orlando, FL, 2015.Google Scholar
  20. 20.
    Sherman SI. Lessons learned and questions unanswered from use of multitargeted kinase inhibitors in medullary thyroid cancer. Oral Oncol. 2013;49:707–10.CrossRefPubMedGoogle Scholar
  21. 21.
    Hu MI, Ying AK, Jimenez C. Update on medullary thyroid cancer. Endocrinol Metab Clin North Am. 2014;43:423–42.CrossRefPubMedGoogle Scholar
  22. 22.
    Capp C, Wajner SM, Siqueira DR, et al. Increased expression of vascular endothelial growth factor and its receptors, VEGFR-1 and VEGFR-2, in medullary thyroid carcinoma. Thyroid. 2010;20:863–71.CrossRefPubMedGoogle Scholar
  23. 23.
    Rodriguez-Antona C, Pallares J, Montero-Conde C, et al. Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis. Endocr Relat Cancer. 2010;17:7–16.CrossRefPubMedGoogle Scholar
  24. 24.
    Sherman SI, Cohen EE, Schoffski P, et al. Efficacy of cabozantinib (Cabo) in medullary thyroid cancer (MTC) patients with RAS or RET mutations: results from a phase III study. J Clin Oncol. 2013;31.Google Scholar
  25. 25.
    Schlumberger M, Elisei R, Muller SP, et al. Final overall survival analysis of EXAM, an international, double-blind, randomized, placebo-controlled phase III trial of cabozantinib (Cabo) in medullary thyroid carcinoma (MTC) patients with documented RECIST progression at baseline. J Clin Oncol. 2015;33.Google Scholar
  26. 26.
    De Falco V, Buonocore P, Muthu M, et al. Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer. J Clin Endocrinol Metab. 2013;98:E811–9.CrossRefPubMedGoogle Scholar
  27. 27.
    NCI: A Phase II Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer. In: clinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 (cited 28 Aug 2015). Available from: https://clinicaltrials.gov/ct2/show/study/NCT01838642?view=record. NLM identifier: NCT01838642.
  28. 28.
    Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372:621–30.CrossRefPubMedGoogle Scholar
  29. 29.
    Takahashi S, Tahara M, Kiyota N, et al: Phase II study of lenvatinib (len), a multi-targeted tyrosine kinase inhibitor, in patients (pts) with all histologic subtypes of advanced thyroid cancer (differentiated, medullary, and anaplastic). Ann Oncol. 2014;25:iv340–56.Google Scholar
  30. 30.
    Schlumberger M, Jarzab B, Cabanillas ME, et al. A Phase 2 trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in advanced medullary thyroid cancer (MTC). Clin Cancer Res. 2015.Google Scholar
  31. 31.
    Carr LL, Mankoff DA, Goulart BH, et al. Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res. 2010;16:5260–8.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    De Souza JA, Busaidy N, Zimrin A, et al. Phase II trial of sunitinib in medullary thyroid cancer (MTC). J Clin Oncol. 2010;28:suppl;abstr 5504.Google Scholar
  33. 33.
    Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82.CrossRefPubMedGoogle Scholar
  34. 34.
    Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774–82.CrossRefPubMedGoogle Scholar
  35. 35.
    EORTC: Nintedanib(BIBF1120) in Thyroid Cancer, pp In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). 2000-(cited 28 Aug). Available from: https://clinicaltrials.gov/ct2/show/NCT01788982. NLM identifier: NCT01788982.
  36. 36.
    Bible KC, Suman VJ, Molina JR, et al. A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. J Clin Endocrinol Metab. 2014;99:1687–93.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Dadu R, Devine C, Hernandez M, et al. Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib. J Clin Endocrinol Metab. 2014;99:2086–94.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Weitzman SP, Peicher KT, Dadu R, et al. Salvage therapy: when a tyrosine kinase inhibitor (TKI) Fails in Advanced Medullary Thyroid Cancer (MTC). Endocr Rev. 2015;36:OR44-4.Google Scholar
  39. 39.
    Cleary JM, Sadow PM, Randolph GW, et al. Neoadjuvant treatment of unresectable medullary thyroid cancer with sunitinib. J Clin Oncol. 2010;28:e390–2.CrossRefPubMedGoogle Scholar
  40. 40.
    Zaytseva YY, Valentino JD, Gulhati P, et al. mTOR inhibitors in cancer therapy. Cancer Lett. 2012;319:1–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci. 2009;122:3589–94.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Menon S, Manning BD. Common corruption of the mTOR signaling network in human tumors. Oncogene. 2008;27(Suppl 2):S43–51.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Lorch J, Busaidy N, Ruan D, et al. A phase II study of everolimus in patients with aggressive RAI refractory (RAIR) thyroid cancer (TC). J Clin Oncol. 2013;31.Google Scholar
  44. 44.
    Baksh K, Weber J. Immune checkpoint protein inhibition for cancer: preclinical justification for CTLA-4 and PD-1 blockade and new combinations. Semin Oncol. 2015;42:363–77.CrossRefPubMedGoogle Scholar
  45. 45.
    Bilusic M, Heery CR, Arlen PM, et al. Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma. Cancer Immunol Immunother. 2014;63:225–34.CrossRefPubMedGoogle Scholar
  46. 46.
    Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol. 1999;17:3631–52.PubMedGoogle Scholar
  47. 47.
    Lam ET, Ringel MD, Kloos RT, et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2010;28:2323–30.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Oncology K. An open label phase II study of tipifarnib in advanced non-hematological malignancies with HRAS mutations. In: clinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-(cited 31 Aug 2015). Available from: https://clinicaltrials.gov/ct2/show/record/NCT02383927. NLM identifier: NCT02383927.
  49. 49.
    Brem GJ, Mylonas I, Bruning A. Eeyarestatin causes cervical cancer cell sensitization to bortezomib treatment by augmenting ER stress and CHOP expression. Gynecol Oncol. 2013;128:383–90.CrossRefPubMedGoogle Scholar
  50. 50.
    Vidula N, Rugo HS. Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Breast Cancer: A Review of Preclinical and Clinical Data. Clin Breast Cancer. 2015.Google Scholar
  51. 51.
    Desai AV, El-Bakkar H, Abdul-Hay M. Novel agents in the treatment of chronic lymphocytic leukemia: a review about the future. Clin Lymphoma Myeloma Leuk. 2015;15:314–22.CrossRefPubMedGoogle Scholar
  52. 52.
    Dadu R, Hu MI, Cleeland CS, et al. The efficacy of the natural clay, Calcium Aluminosilicate Anti-Diarrheal (CASAD), in reducing medullary thyroid cancer-related diarrhea and its effects on quality of life: a pilot study. Thyroid 2015.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Jessica E. Zwiener
    • 1
  • Lily J. Kwatampora
    • 2
  • Naifa L. Busaidy
    • 1
  1. 1.Department of Endocrine Neoplasia and Hormonal DisordersMD Anderson Cancer Center, The University of TexasHoustonUSA
  2. 2.Endocrinology Diabetes and MetabolismBaylor College of MedicineHoustonUSA

Personalised recommendations