Skip to main content

Advertisement

Log in

The experience of an Endocrinology Division on the use of tyrosine multikinase inhibitor therapy in patients with radioiodine-resistant differentiated thyroid cancer

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

To describe the experience of our Division of Endocrinology with multikinase inhibitor (MKI) treatment in radioiodine-resistant differentiated thyroid cancer (DTC) patients.

Methods

Adults patients with a diagnosis of DTC treated with an MKI drug from March 2011 to October 2018 were registered into a retrospective database. Primary objectives were: the assessment of progression-free survival (PFS) and radiographic response evaluated according to RECIST v. 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v. 5.0.

Results

Twenty-two patients were treated with MKIs (21 with sorafenib, one with lenvatinib as first-line treatment). Seven patients required a second-line therapy with lenvatinib and one patient required a third-line treatment with pazopanib. Median duration of treatment was 11.2 (4.8–79.6) months. Best responses with sorafenib were partial response (PR) in two patients (11%), stable disease (SD) >6 months in 13 patients (72%), and progressive disease (PD) in three patients (17%). Best responses with second-line lenvatinib were PR in one patient (33%) and SD in two patients (66%). Median PFS was 31.5 months. AEs were present in 19 (90%) patients under sorafenib. The most common AEs were hand–foot syndrome (HFS) (67%), diarrhea (52%), and hypertension (52%). Definitive withdrawal was necessary in only one patient (4.7%).

Conclusions

Our study reflects the real-world clinical experience of an Endocrinology Division on the management of radioiodine-resistant DTC patients with sorafenib and lenvatinib, showing a beneficial therapeutic effect with acceptable tolerability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. C. Durante, N. Haddy, E. Baudin, S. Leboulleux, D. Hartl, J.P. Travagli, B. Caillou, M. Ricard, J.D. Lumbroso, F. De Vathaire, M. Schlumberger, 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. 91, 2892–2899 (2006)

    Article  CAS  PubMed  Google Scholar 

  2. A. Albero, J.E. Lopez, A. Torres, L. de la Cruz, T. Martin, Effectiveness of chemotherapy in advanced differentiated thyroid cancer: a systematic review. Endocr. Relat. Cancer 23, R71–R84 (2016)

    Article  CAS  PubMed  Google Scholar 

  3. M.S. Brose, C.M. Nutting, B. Jarzab, R. Elisei, S. Siena, L. Bastholt, C. de la Fouchardiere, F. Pacini, R. Paschke, Y.K. Shong, S. Sherman, J.W. Smit, J. Chung, C. Kappeler, C. Peña, I. Molnár, M.J. Schlumberger, Sorafenib in locally advanced or metastatic, radioactive iodine- refractory, differentiated thyroid cancer: a randomized, double- blind, phase 3. DECISION trial. Lancet 384, 319–328 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. M. Schlumberger, M. Tahara, L.J. Wirth, B. Robinson, M.S. Brose, R. Elisei, M.A. Habra, K. Newbold, M.H. Shah, A.O. Hoff, A.G. Gianoukakis, N. Kiyota, M.H. Taylor, S.B. Kim, M.K. Krzyzanowska, C.E. Dutcus, B. de las Heras, J. Zhu, S.I. Sherman, Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N. Engl. J. Med. 372, 621–630 (2015)

    Article  CAS  PubMed  Google Scholar 

  5. E.E. Cohen, L.S. Rosen, E.E. Vokes, M.S. Kies, A.A. Forastiere, F.P. Worden, M.A. Kane, E. Sherman, S. Kim, P. Bycott, M. Tortorici, D.R. Shalinsky, K.F. Liau, R.B. Cohen, Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J. Clin. Oncol. 26, 4708–4713 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. K.C. Bible, V.J. Suman, J.R. Molina, R.C. Smallridge, W.J. Maples, M.E. Menefee, J. Rubin, K. Sideras, J.C. Morris III., B. McIver, J.K. Burton, K.P. Webster, C. Bieber, A.M. Traynor, P.J. Flynn, B.C. Goh, H. Tang, S.P. Ivy, C. Erlichman, Efficacy of pazopanib in progressive, radioiodine refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 11, 962–972 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. L.L. Carr, D.A. Mankoff, B.H. Goulart, K.D. Eaton, P.T. Capell, E.M. Kell, J.E. Bauman, R.G. Martins, 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. 16, 5260–5268 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. M.E. Cabanillas, J.A. de Souza, S. Geyer, L.J. Wirth, M.E. Menefee, S.V. Liu, K. Shah, J. Wright, M.H. Shah, Cabozantinib as salvage therapy for patients with tyrosine kinase inhibitor-refractory differentiated thyroid cancer: results of a Multicenter Phase II International Thyroid Oncology Group Trial. J. Clin. Oncol. 35, 3315–3321 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. B.R. Haugen, E.K. Alexander, K.C. Bible, G. Doherty, S.J. Mandel, Y.E. Nikiforov, F. Pacini, G. Randolph, A. Sawka, M. Schlumberger, K.G. Schuff, S.I. Sherman, J.A. Sosa, D. Steward, R.M. Tuttle, L. Wartofsky, 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid 26, 1–133 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  10. M.S. Brose, J. Smit, C.C. Lin, F. Pitoia, M. Fellous, Y. DeSanctis, M. Schlumberger, M. Tori, I. Sugitani, Timing of multikinase inhibitor initiation in differentiated thyroid cancer. Endocr. Relat. Cancer 24, 237–242 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. M. Schlumberger, M. Brose, R. Elisei, S. Leboulleux, M. Luster, F. Pitoia, F. Pacini, Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol. 2, 356–358 (2014)

    Article  PubMed  Google Scholar 

  12. E.A. Eisenhauer, P. Therasse, J. Bogaerts, L.H. Schwartz, D. Sargent, R. Ford, J. Dancey, S. Arbuck, S. Gwyther, M. Mooney, L. Rubinstein, L. Shankar, L. Dodd, R. Kaplan, D. Lacombe, J. Verweij, New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228–247 (2009)

    Article  CAS  Google Scholar 

  13. National Cancer Institute. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf. Accessed 09 Oct 2018

  14. M.E. Cabanillas, S.G. Waguespack, Y. Bronstein, M.D. Williams, L. Feng, M. Hernandez, A. Lopez, S.I. Sherman, N.L. Busaidy, Treatment with tyrosine kinase inhibitors for patients with differentiated thyroid cancer: the M. D. Anderson experience. J. Clin. Endocrinol. Metab. 95, 2588–2595 (2010)

    Article  CAS  PubMed  Google Scholar 

  15. M. Molina-Vega, J. García-Alemán, A. Sebastián-Ochoa, I. Mancha-Doblas, J.M. Trigo-Pérez, F. Tinahones-Madueño, Tyrosine kinase inhibitors in iodine-refractory differentiated thyroid cancer: experience in clinical practice. Endocrine 59, 395–401 (2018)

    Article  CAS  PubMed  Google Scholar 

  16. M.H. Massicotte, M. Brassard, M. Claude-Desroches, I. Borget, F. Bonichon, A.L. Giraudet, C. Do Cao, C.N. Chougnet, S. Leboulleux, E. Baudin, M. Schlumberger, C. de la Fouchardière, Tyrosine kinase inhibitor treatments in patients with metastatic thyroid carcinomas: a retrospective study of the TUTHYREF network. Eur. J. Endocrinol. 170, 575–582 (2014)

    Article  CAS  PubMed  Google Scholar 

  17. R. Dadu, C. Devine, M. Hernandez, S.G. Waguespack, N.L. Busaidy, M.I. Hu, C. Jimenez, M.A. Habra, R.V. Sellin, A.K. Ying, G.J. Cote, S.I. Sherman, M.E. Cabanillas, Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib. J. Clin. Endocrinol. Metab. 99, 2086–2094 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. R. Copher, O. Adejoro, S.D. Byfield, M. DuCharme, D. Chatterjee, P.R. Joshi, A. Desai, M.A. Baig, Second or none: many patients treated for refractory differentiated thyroid cancer with small molecular kinase inhibitors do not receive a second line of therapy. J. Clin. Oncol. 35(15_suppl), e17589 (2017)

  19. R.P. Dang, D. McFarland, V.H. Le, N. Camille, B.A. Miles, M.S. Teng, E.M. Genden, K.J. Misiukiewicz, Neoadjuvant therapy in differentiated thyroid cancer. Int. J. Surg. Oncol. 2016, 3743420 (2016)

    PubMed  PubMed Central  Google Scholar 

  20. D.L.S. Danilovic, G. Castro Jr., F.S.R. Roitberg, F.A.B. Vanderlei, F.A. Bonani, R.M.C. Freitas, G.B. Coura-Filho, R.Y. Camargo, M.A. Kulcsar, S. Marui, A.O. Hoff, Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer. Arch. Endocrinol. Metab. 62, 370–375 (2018)

    Article  PubMed  Google Scholar 

  21. M.S. Brose, C.T. Frenette, S.M. Keefe, S.M. Stein, Management of sorafenib-related adverse events: a clinician’s perspective. Semin. Oncol. 41, S1–S16 (2014)

    Article  PubMed  Google Scholar 

  22. T.E. Hutson, J. Bellmunt, C. Porta, C. Szczylik, M. Staehler, A. Nadel, S. Anderson, R. Bukowski, T. Eisen, B. Escudier; Sorafenib TARGET Clinical Trial Group, Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur. J. Cancer 46, 2432–2440 (2010)

    Article  CAS  PubMed  Google Scholar 

  23. W.X. Qi, Z. Shen, L.N. Tang, Y. Yao, Congestive heart failure risk in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors: a systematic review and meta-analysis of 36 clinical trials. Br. J. Clin. Pharmacol. 78, 748–762 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fabián Pitoia.

Ethics declarations

Conflict of interest

Fabián Pitoia is medical advisor, speaker and Steering Committee Bayer. Consultancy for Sanofi and Raffo Laboratories. The remaining authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Institutional Review Board.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jerkovich, F., García Falcone, M.G. & Pitoia, F. The experience of an Endocrinology Division on the use of tyrosine multikinase inhibitor therapy in patients with radioiodine-resistant differentiated thyroid cancer. Endocrine 64, 632–638 (2019). https://doi.org/10.1007/s12020-019-01883-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-019-01883-3

Keywords

Navigation