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Notwithstanding regulatory approval of lenvatinib and sorafenib to treatradioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC),important questions and controversies persist regarding this use of thesetyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiaryreferral centers convened to identify and explore such issues; this papersummarizes their discussions. One challenge is determining when to start TKItherapy. Decision-making should be shared between patients andmultidisciplinary caregivers, and should consider tumor size/burden,growth rate, and site(s), the key drivers of RAI-R DTC morbidity andmortality, along with current and projected tumor-related symptomatology,co-morbidities, and performance status. Another question involves choice offirst-line TKIs. Currently, lenvatinib is generally preferred, due togreater increase in progression-free survival versus placebo treatment andhigher response rate in its pivotal trial versus that of sorafenib;additionally, in those studies, lenvatinib but not sorafenib showed overallsurvival benefit in subgroup analysis. Whether recommended maximum or lowerTKI starting doses better balance anti-tumor effects versus tolerability isalso unresolved. Exploratory analyses of lenvatinib pivotal study datasuggest dose-response effects, possibly favoring higher dosing; however,results are awaited of a prospective comparison of lenvatinib startingregimens. Some controversy surrounds determination of net therapeuticbenefit, the key criterion for continuing TKI therapy: if tolerability isacceptable, overall disease control may justify further treatment despitelimited but manageable progression. Future research should assess potentialguideposts for starting TKIs; fine-tune dosing strategies and furthercharacterize antitumor efficacy; and evaluate interventions to preventand/or treat TKI toxicity, particularly palmar-plantarerythrodysesthesia and fatigue.

hormone and metabolic research

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