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CC BY-NC-ND 4.0 · Horm Metab Res 2021; 53(03): 149-160
DOI: 10.1055/a-1380-4154
Review

Questions and Controversies in the Clinical Application of Tyrosine Kinase Inhibitors to Treat Patients with Radioiodine-Refractory Differentiated Thyroid Carcinoma: Expert Perspectives

Frederik A. Verburg
1   Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany
2   Erasmus Medical Center, Department of Radiology and Nuclear Medicine, Rotterdam, The Netherlands
,
Holger Amthauer
3   Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nuclear Medicine, Berlin, Germany
,
Ina Binse†   †
4   Department of Nuclear Medicine, University Clinic Essen, Essen, Germany
,
Ingo Brink
5   Department of Medical Diagnostics and Therapy, Ernst von Bergmann Hospital Potsdam, Potsdam, Germany
,
Andreas Buck
6   Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
,
Andreas Darr
7   Department of Nuclear Medicine, University Hospital Jena, Jena, Germany
,
Christine Dierks
8   Department of Medical Oncology, University Hospital Freiburg, Freiburg, Germany
,
Christine Koch
9   Department of Gastroenterology, Hepatology, and Endocrinology, University Clinic Frankfurt, Frankfurt Am Main, Germany
,
Ute König
10   Department of Gastroenterology and Endocrinology, University of Göttingen, Göttingen, Germany
,
Michael C. Kreissl
11   Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Otto von Guericke University Magdeburg, Magdeburg, Germany
,
Markus Luster
1   Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany
,
Christoph Reuter
12   Department of Palliative Care, Hannover Medical School, Hannover, Germany
,
Klemens Scheidhauer
13   Interdisclipinary Endocrine Center, Technical University of Munich, Munich, Germany
,
Holger Sven Willenberg 
14   Division of Endocrinology and Metabolism, Medical University of Rostock, Rostock, Germany
,
Andreas Zielke
15   Department of Endocrine Surgery, Diakonie Klinikum Stuttgart, Stuttgart, Germany
,
Matthias Schott
16   Division of Endocrinology, University Hospital Düsseldorf, Düsseldorf, Germany
› Institutsangaben
Funding Eisai GmbH, Frankfurt, Germany.
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Abstract

Notwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.

Key words

multi-kinase inhibitors - treatment initiation and discontinuation - dosing - second-line therapy - lenvatinib - sorafenib

† In memoriam. This paper is dedicated to the memory of our colleague, Dr. Ina Binse, who passed away during the development of the manuscript.


Supplementary Material



Publikationsverlauf

Eingereicht: 26. April 2020

Angenommen nach Revision: 26. Januar 2021

Artikel online veröffentlicht:
02. März 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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