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; Holger Amthauer; Ina Binse; Ingo Brink; Andreas Buck; Andreas Darr; Christine Dierks; Christine Koch; Ute König; Michael C. Kreissl; Markus Luster; Christoph Reuter; Klemens Scheidhauer; Holger Sven Willenberg; Andreas Zielke; Matthias Schott

doi:10.1055/a-1380-4154

Hormone and Metabolic Research, Inhaltsverzeichnis

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

¹Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

²Erasmus Medical Center, Department of Radiology and Nuclear Medicine, Rotterdam, The Netherlands

,

Holger Amthauer

³Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nuclear Medicine, Berlin, Germany

,

Ina Binse†^†

⁴Department of Nuclear Medicine, University Clinic Essen, Essen, Germany

,

Ingo Brink

⁵Department of Medical Diagnostics and Therapy, Ernst von Bergmann Hospital Potsdam, Potsdam, Germany

,

Andreas Buck

⁶Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany

,

Andreas Darr

⁷Department of Nuclear Medicine, University Hospital Jena, Jena, Germany

,

Christine Dierks

⁸Department of Medical Oncology, University Hospital Freiburg, Freiburg, Germany

,

Christine Koch

⁹Department of Gastroenterology, Hepatology, and Endocrinology, University Clinic Frankfurt, Frankfurt Am Main, Germany

,

Ute König

¹⁰Department of Gastroenterology and Endocrinology, University of Göttingen, Göttingen, Germany

,

Michael C. Kreissl

¹¹Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Otto von Guericke University Magdeburg, Magdeburg, Germany

,

Markus Luster

¹Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

,

Christoph Reuter

¹²Department of Palliative Care, Hannover Medical School, Hannover, Germany

,

Klemens Scheidhauer

¹³Interdisclipinary Endocrine Center, Technical University of Munich, Munich, Germany

,

Holger Sven Willenberg

¹⁴Division of Endocrinology and Metabolism, Medical University of Rostock, Rostock, Germany

,

Andreas Zielke

¹⁵Department of Endocrine Surgery, Diakonie Klinikum Stuttgart, Stuttgart, Germany

,

Matthias Schott

¹⁶Division of Endocrinology, University Hospital Düsseldorf, Düsseldorf, Germany

› Institutsangaben

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

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Referenzen

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