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