Skip to main content
Top
Published in: Endocrine 3/2019

01-06-2019 | Lenvatinib | Original Article

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

Authors: Fernando Jerkovich, María Gabriela García Falcone, Fabián Pitoia

Published in: Endocrine | Issue 3/2019

Login to get access

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.
Literature
1.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
2.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
3.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
4.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
5.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
6.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
7.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
8.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
9.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
10.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
11.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
12.
go back to reference 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)CrossRef 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)CrossRef
14.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
15.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
16.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
17.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
18.
go back to reference 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) 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.
go back to reference 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)PubMedPubMedCentral 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)PubMedPubMedCentral
20.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
21.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
22.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
23.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
Metadata
Title
The experience of an Endocrinology Division on the use of tyrosine multikinase inhibitor therapy in patients with radioiodine-resistant differentiated thyroid cancer
Authors
Fernando Jerkovich
María Gabriela García Falcone
Fabián Pitoia
Publication date
01-06-2019
Publisher
Springer US
Published in
Endocrine / Issue 3/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-019-01883-3

Other articles of this Issue 3/2019

Endocrine 3/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.