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Published in: Endocrine 3/2021

01-09-2021 | Lenvatinib | Original Article

Late toxicities burden in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib

Authors: F. Platini, S. Cavalieri, S. Alfieri, C. Bergamini, C. Resteghini, A. Bottiglieri, E. Colombo, L. Mazzeo, L. Licitra, B. Paolini, E. Seregni, L. D. Locati

Published in: Endocrine | Issue 3/2021

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Abstract

Purpose

Radioactive-iodine (RAI)-resistant differentiated thyroid cancer (DTC) patients benefit from multi-kinase inhibitors (MKIs), such as lenvatinib. Incidence of treatment-related (TR) late toxicities has been not yet described.

Methods

From January 2015 to June 2019 we retrospectively reviewed clinical records of patients with RAI-resistant DTC treated with lenvatinib at Istituto Nazionale dei Tumori (Milan, Italy). New side effect of any grade, appeared after 12 months of lenvatinib, was defined as late adverse event (AE). Descriptive analyses were performed. Survival curves were estimated with Kaplan–Meier method and compared with log-rank test.

Results

Thirty-seven patients were included, 65% had ≥65 years and 68% were female. Thirty patients received lenvatinib for >12 months. Lenvatinib was started at ≤20 mg/daily in 59% of patients, 64% were ≥65 years. The frequency of late AEs was 80% and cardiovascular toxicity was the most common (57%). There was no difference in the incidence of late AEs between younger/older population (77% and 82%, respectively). Median lenvatinib treatment duration (TD) was 39.96 months (95% CI 21.64-NR): 39.96 months for patients <65 years (95% CI: 13.25-NR) and 37.53 months for those ≥65 years, respectively (95% CI: 15.85-NR). Median overall survival (OS) was 39.96 months (95% CI: 21.84-NR), no statistically differences in OS was observed between younger (<65 years) and older patients (≥65 years) (HR 1.013; 95% CI 0.963–1.065; p = 0.62).

Conclusion

Late toxicity burden of lenvatinib is not negligible. Cardiovascular toxicity remains the principal side effect even after a prolonged lenvatinib exposition.
Literature
2.
go back to reference M. Schlumberger, M. Tahara, L.J. Wirth et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N. Engl. J. Med. 372(7), 621–630 (2015)CrossRef M. Schlumberger, M. Tahara, L.J. Wirth et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N. Engl. J. Med. 372(7), 621–630 (2015)CrossRef
3.
go back to reference M.S. Brose, C.M. Nutting, B. Jarzab et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomized, double-blind, phase 3 trial. Lancet 384(9940), 319–328 (2014)CrossRef M.S. Brose, C.M. Nutting, B. Jarzab et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomized, double-blind, phase 3 trial. Lancet 384(9940), 319–328 (2014)CrossRef
4.
go back to reference R.I. Haddad, M. Schlumberger, L.J. Wirth et al. Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes. Endocrine 56(1), 121–128 (2017)CrossRef R.I. Haddad, M. Schlumberger, L.J. Wirth et al. Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes. Endocrine 56(1), 121–128 (2017)CrossRef
6.
go back to reference A. Nervo, M. Gallo, M.T. Samà et al. Lenvatinib in Advanced Radioiodine-refractory Thyroid Cancer: a Snapshot of Real-life Clinical Practice. Anticancer Res. 38(3), 1643–1649 (2018)PubMed A. Nervo, M. Gallo, M.T. Samà et al. Lenvatinib in Advanced Radioiodine-refractory Thyroid Cancer: a Snapshot of Real-life Clinical Practice. Anticancer Res. 38(3), 1643–1649 (2018)PubMed
7.
go back to reference L.D. Locati, A. Piovesan, C. Durante et al. Real-world efficacy and safety of lenvatinib: data from a compassionate use in the treatment of radioactive iodine-refractory differentiated thyroid cancer patients in Italy. Eur. J. Cancer 118, 35–40 (2019)CrossRef L.D. Locati, A. Piovesan, C. Durante et al. Real-world efficacy and safety of lenvatinib: data from a compassionate use in the treatment of radioactive iodine-refractory differentiated thyroid cancer patients in Italy. Eur. J. Cancer 118, 35–40 (2019)CrossRef
8.
go back to reference F. Jerkovich, I. Califano, F. Bueno et al. Real-life use of lenvatinib in patients with differentiated thyroid cancer: experience from Argentina. Endocrine 69(1), 142–148 (2020)CrossRef F. Jerkovich, I. Califano, F. Bueno et al. Real-life use of lenvatinib in patients with differentiated thyroid cancer: experience from Argentina. Endocrine 69(1), 142–148 (2020)CrossRef
9.
go back to reference E.V. Borodavina, P. Isaev, A. Shurinov, V. Krylov, Efficacy and tolerability of lenvatinib in patients with radioiodine-refractory differentiated thyroid Cancer: results a multicentre observational study Russian Federation. Head Neck Tumours 10, 65–72 (2020)CrossRef E.V. Borodavina, P. Isaev, A. Shurinov, V. Krylov, Efficacy and tolerability of lenvatinib in patients with radioiodine-refractory differentiated thyroid Cancer: results a multicentre observational study Russian Federation. Head Neck Tumours 10, 65–72 (2020)CrossRef
11.
go back to reference B.R. Haugen, E.K. Alexander, K.C. Bible et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 26(1), 1–133 (2016)CrossRef B.R. Haugen, E.K. Alexander, K.C. Bible et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 26(1), 1–133 (2016)CrossRef
12.
go back to reference S. Filetti, C. Durante, D. Hartl et al. ESMO Guidelines Committee. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 30(12), 1856–1883 (2019)CrossRef S. Filetti, C. Durante, D. Hartl et al. ESMO Guidelines Committee. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 30(12), 1856–1883 (2019)CrossRef
13.
go back to reference M.E. Cabanillas, D.G. McFadden, C. Durante, Thyroid Cancer Lancet 388(10061), 2783–2795 (2016)PubMed M.E. Cabanillas, D.G. McFadden, C. Durante, Thyroid Cancer Lancet 388(10061), 2783–2795 (2016)PubMed
14.
go back to reference L.J. Wirth, M. Tahara, B. Robinson et al. Treatment-emergent hypertension and efficacy in the phase 3 Study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT). Cancer 124(11), 2365–2372 (2018)CrossRef L.J. Wirth, M. Tahara, B. Robinson et al. Treatment-emergent hypertension and efficacy in the phase 3 Study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT). Cancer 124(11), 2365–2372 (2018)CrossRef
15.
go back to reference J.F. Piccirillo, Importance of comorbidity in head and neck cancer. Laryngoscope 110(4), 593–602 (2000)CrossRef J.F. Piccirillo, Importance of comorbidity in head and neck cancer. Laryngoscope 110(4), 593–602 (2000)CrossRef
16.
go back to reference M. Schlumberger, M. Brose, R. Elisei et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol. 2(5), 356–358 (2014)CrossRef M. Schlumberger, M. Brose, R. Elisei et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol. 2(5), 356–358 (2014)CrossRef
17.
go back to reference M. Tahara, M.S. Brose, L.J. Wirth et al. Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study in patients with radioiodine-refractory differentiated thyroid cancer. Eur. J. Cancer 106, 61–68 (2019)CrossRef M. Tahara, M.S. Brose, L.J. Wirth et al. Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study in patients with radioiodine-refractory differentiated thyroid cancer. Eur. J. Cancer 106, 61–68 (2019)CrossRef
18.
go back to reference L. Paschke, T. Lincke, K. Mühlberg, T.H. Lindner, R. Paschke, Myocardial Infarction after Long-Term Treatment with a Tyrosine Kinase Inhibitor (TKI) with Anti-VEGF Receptor Activity. Case Rep. Endocrinol. 2019, 7927450 (2019)PubMedPubMedCentral L. Paschke, T. Lincke, K. Mühlberg, T.H. Lindner, R. Paschke, Myocardial Infarction after Long-Term Treatment with a Tyrosine Kinase Inhibitor (TKI) with Anti-VEGF Receptor Activity. Case Rep. Endocrinol. 2019, 7927450 (2019)PubMedPubMedCentral
19.
go back to reference A. Ravaud, C. de la Fouchardière, P. Caron et al. A multicenter phase II study of sunitinib in patients with locally advanced or metastatic differentiated, anaplastic or medullary thyroid carcinomas: mature data from the THYSU study. Eur. J. Cancer 76, 110–117 (2017)CrossRef A. Ravaud, C. de la Fouchardière, P. Caron et al. A multicenter phase II study of sunitinib in patients with locally advanced or metastatic differentiated, anaplastic or medullary thyroid carcinomas: mature data from the THYSU study. Eur. J. Cancer 76, 110–117 (2017)CrossRef
20.
go back to reference G. Curigliano, D. Lenihan, M. Fradley et al. ESMO Guidelines Committee. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann. Oncol. 31(2), 171–190 (2020)CrossRef G. Curigliano, D. Lenihan, M. Fradley et al. ESMO Guidelines Committee. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann. Oncol. 31(2), 171–190 (2020)CrossRef
21.
go back to reference S. Cavalieri, L. Cosmai, A. Genderini et al. Lenvatinib-induced renal failure: two first-time case reports and review of literature. Expert Opin. Drug Metab. Toxicol. 14(4), 379–385 (2018)CrossRef S. Cavalieri, L. Cosmai, A. Genderini et al. Lenvatinib-induced renal failure: two first-time case reports and review of literature. Expert Opin. Drug Metab. Toxicol. 14(4), 379–385 (2018)CrossRef
22.
go back to reference C. Resteghini, S. Cavalieri, D. Galbiati et al. Management of tyrosine kinase inhibitors (TKI) side effects in differentiated and medullary thyroid cancer patients. Best. Pr. Res. Clin. Endocrinol. Metab. 31(3), 349–361 (2017)CrossRef C. Resteghini, S. Cavalieri, D. Galbiati et al. Management of tyrosine kinase inhibitors (TKI) side effects in differentiated and medullary thyroid cancer patients. Best. Pr. Res. Clin. Endocrinol. Metab. 31(3), 349–361 (2017)CrossRef
23.
go back to reference M. Sanda, H. Tamai, H. Deguchi et al. Acalculous cholecystitis in a patient with hepatocellular carcinoma on sorafenib. ISRN Gastroenterol. 2011, 201529 (2011)PubMed M. Sanda, H. Tamai, H. Deguchi et al. Acalculous cholecystitis in a patient with hepatocellular carcinoma on sorafenib. ISRN Gastroenterol. 2011, 201529 (2011)PubMed
24.
go back to reference Y. Aihara, H. Yoshiji, M. Yamazaki et al. A case of severe acalculous cholecystitis associated with sorafenib treatment for advanced hepatocellular carcinoma. World J. Gastrointest. Oncol. 4(5), 115–118 (2012)CrossRef Y. Aihara, H. Yoshiji, M. Yamazaki et al. A case of severe acalculous cholecystitis associated with sorafenib treatment for advanced hepatocellular carcinoma. World J. Gastrointest. Oncol. 4(5), 115–118 (2012)CrossRef
25.
go back to reference J. Song, S.B. Kim, K.H. Kim, T.N. Kim, K.H. Lee, A case report of motesanib-induced biliary sludge formation causing obstructive cholangitis with acute pancreatitis treated by endoscopic sphincterotomy. Med. (Baltim.) 95(37), e4645 (2016)CrossRef J. Song, S.B. Kim, K.H. Kim, T.N. Kim, K.H. Lee, A case report of motesanib-induced biliary sludge formation causing obstructive cholangitis with acute pancreatitis treated by endoscopic sphincterotomy. Med. (Baltim.) 95(37), e4645 (2016)CrossRef
26.
go back to reference K. Ishigaki, T. Hamada, Y. Nakai et al. Lenvatinib-induced acute acalculous cholecystitis in a patient with hepatocellular carcinoma. Clin. J. Gastroenterol. 13(4), 568–571 (2020)CrossRef K. Ishigaki, T. Hamada, Y. Nakai et al. Lenvatinib-induced acute acalculous cholecystitis in a patient with hepatocellular carcinoma. Clin. J. Gastroenterol. 13(4), 568–571 (2020)CrossRef
27.
go back to reference A. Nervo, A. Ragni, M. Gallo et al. Symptomatic Biliary Disorders During Lenvatinib Treatment for Thyroid Cancer: an Underestimated Problem. Thyroid 30(2), 229–236 (2020)CrossRef A. Nervo, A. Ragni, M. Gallo et al. Symptomatic Biliary Disorders During Lenvatinib Treatment for Thyroid Cancer: an Underestimated Problem. Thyroid 30(2), 229–236 (2020)CrossRef
28.
go back to reference C. Colombo, S. De Leo, M. Di Stefano, G. Vannucchi, L. Persani, L. Fugazzola, Primary Adrenal Insufficiency During Lenvatinib or Vandetanib and Improvement of Fatigue After Cortisone Acetate Therapy. J. Clin. Endocrinol. Metab. 104(3), 779–784 (2019)CrossRef C. Colombo, S. De Leo, M. Di Stefano, G. Vannucchi, L. Persani, L. Fugazzola, Primary Adrenal Insufficiency During Lenvatinib or Vandetanib and Improvement of Fatigue After Cortisone Acetate Therapy. J. Clin. Endocrinol. Metab. 104(3), 779–784 (2019)CrossRef
29.
go back to reference J.D. Cox, J. Stetz, T.F. Pajak, Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J. Radiat. Oncol. Biol. Phys. 31(5), 1341–1346 (1995)CrossRef J.D. Cox, J. Stetz, T.F. Pajak, Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J. Radiat. Oncol. Biol. Phys. 31(5), 1341–1346 (1995)CrossRef
30.
go back to reference J.A. Langendijk, P. Doornaert, Verdonck-de Leeuw IM, Leemans CR, Aaronson NK, Slotman BJ. Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J. Clin. Oncol. 26(22), 3770–3776 (2008)CrossRef J.A. Langendijk, P. Doornaert, Verdonck-de Leeuw IM, Leemans CR, Aaronson NK, Slotman BJ. Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J. Clin. Oncol. 26(22), 3770–3776 (2008)CrossRef
31.
go back to reference G. Thanarajasingam, P.J. Atherton, P.J. Novotny, C.L. Loprinzi, J.A. Sloan, A. Grothey, Longitudinal adverse event assessment in oncology clinical trials: the Toxicity over Time (ToxT) analysis of Alliance trials NCCTG N9741 and 979254. Lancet Oncol. 17(5), 663e70 (2016)CrossRef G. Thanarajasingam, P.J. Atherton, P.J. Novotny, C.L. Loprinzi, J.A. Sloan, A. Grothey, Longitudinal adverse event assessment in oncology clinical trials: the Toxicity over Time (ToxT) analysis of Alliance trials NCCTG N9741 and 979254. Lancet Oncol. 17(5), 663e70 (2016)CrossRef
32.
go back to reference A. Hochhaus, S.G. O’Brien, F. Guilhot et al. Six-year follow-up of patients receiving imatinib for the first line treatment of chronic myeloid leukemia. Leukemia 23, 1054–1061 (2009)CrossRef A. Hochhaus, S.G. O’Brien, F. Guilhot et al. Six-year follow-up of patients receiving imatinib for the first line treatment of chronic myeloid leukemia. Leukemia 23, 1054–1061 (2009)CrossRef
33.
go back to reference C. Giani, L. Valerio, A. Bongiovanni et al. Safety and Quality-of-Life Data from an Italian Expanded Access Program of Lenvatinib for Treatment of Thyroid Cancer. Thyroid 31(2), 224–232 (2021)CrossRef C. Giani, L. Valerio, A. Bongiovanni et al. Safety and Quality-of-Life Data from an Italian Expanded Access Program of Lenvatinib for Treatment of Thyroid Cancer. Thyroid 31(2), 224–232 (2021)CrossRef
34.
go back to reference T.H. Brümmendorf, J.E. Cortes, C.A. de Souza et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronicmyeloid leukaemia: results from the 24-month follow-up of the BELA trial. Br. J. Haematol. 168, 69–81 (2014)CrossRef T.H. Brümmendorf, J.E. Cortes, C.A. de Souza et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronicmyeloid leukaemia: results from the 24-month follow-up of the BELA trial. Br. J. Haematol. 168, 69–81 (2014)CrossRef
35.
go back to reference E. Jabbour, H.M. Kantarjian, G. Saglio et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year followup from a randomized phase 3 trial (DASISION). Blood 123, 494–500 (2014)CrossRef E. Jabbour, H.M. Kantarjian, G. Saglio et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year followup from a randomized phase 3 trial (DASISION). Blood 123, 494–500 (2014)CrossRef
36.
go back to reference R.A. Larson, A. Hochhaus, T.P. Hughes et al. Nilotinib vs. imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 26, 2197–2203 (2012)CrossRef R.A. Larson, A. Hochhaus, T.P. Hughes et al. Nilotinib vs. imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 26, 2197–2203 (2012)CrossRef
37.
go back to reference M.S. Marcolino, E. Boersma, N.C.D. Clementino et al. Imatinib treatment duration is related to decreased estimated glomerular filtration rate in chronic myeloid leukemia patients. Ann. Oncol. 22, 2073–2079 (2011)CrossRef M.S. Marcolino, E. Boersma, N.C.D. Clementino et al. Imatinib treatment duration is related to decreased estimated glomerular filtration rate in chronic myeloid leukemia patients. Ann. Oncol. 22, 2073–2079 (2011)CrossRef
38.
go back to reference M.S. Brose, F.P. Worden, K.L. Newbold, M. Guo, A. Hurria, 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. 35(23), 2692–2699 (2017)CrossRef M.S. Brose, F.P. Worden, K.L. Newbold, M. Guo, A. Hurria, 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. 35(23), 2692–2699 (2017)CrossRef
Metadata
Title
Late toxicities burden in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib
Authors
F. Platini
S. Cavalieri
S. Alfieri
C. Bergamini
C. Resteghini
A. Bottiglieri
E. Colombo
L. Mazzeo
L. Licitra
B. Paolini
E. Seregni
L. D. Locati
Publication date
01-09-2021
Publisher
Springer US
Published in
Endocrine / Issue 3/2021
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-021-02702-4

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