Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial

Naomi Kiyota, Bruce Robinson, Manisha Shah, Ana O. Hoff, Matthew H. Taylor, Di Li, Corina E. Dutcus, Eun Kyung Lee, Sung Bae Kim, Makoto Tahara

    Research output: Contribution to journalArticle

    12 Scopus citations

    Abstract

    Background: While there is a clear consensus for defining radioiodine-refractory differentiated thyroid cancer (RR-DTC), it is unknown whether these criteria are equally valid for determining when radioiodine (RAI) therapy is no longer beneficial and systemic treatment should be considered. Lenvatinib, a multikinase inhibitor, significantly prolonged progression-free survival (PFS) compared to placebo in a Phase 3 trial in RR-DTC (SELECT; hazard ratio [HR]: 0.21 [99% confidence interval (CI) 0.14-0.31]; p < 0.001). This sub-analysis compared clinical outcomes of lenvatinib-treated patients in SELECT stratified by RR-DTC inclusion criteria. Methods: In SELECT, patients with measurable RR-DTC and radiologic evidence of disease progression ≤13 months prior to study entry were randomized 2:1 to lenvatinib (24 mg/day; 28-day cycle) or placebo. In this analysis, patients were stratified based on the following RR-DTC inclusion criteria: no RAI uptake, disease progression within 12 months of RAI therapy despite RAI avidity at the time of treatment, and extensive (>600 mCi) cumulative RAI exposure. All had disease progression as an inclusion criterion for SELECT. Results: Of 392 patients (261 lenvatinib; 131 placebo) enrolled, 275, 235, and 73 patients met the inclusion criteria for no RAI uptake, disease progression despite RAI avidity, and extensive RAI exposure, respectively. There was significant overlap between the patient groups, with 167 (42.6%) patients meeting more than one inclusion criterion. Lenvatinib improved median PFS compared to placebo in all groups ("no RAI uptake": lenvatinib not quantifiable [NQ; CI 14.8-NQ] vs. placebo, 3.7 months [CI 2.5-5.3]; "disease progression despite RAI avidity": lenvatinib 16.5 months [CI 12.8-NQ] vs. placebo, 3.7 months [CI 1.9-5.4]; "extensive RAI exposure": lenvatinib 18.7 months [CI 10.7-NQ] vs. placebo, 3.6 months [CI 1.9-5.5]). Objective response rates were 71.8%, 60.0%, and 56.0% for patients with no RAI uptake, disease progression despite RAI avidity, and extensive RAI exposure, respectively. Lenvatinib-related adverse events were similar across groups. Conclusions: Comparable efficacy and safety profiles were observed in lenvatinib-treated patients regardless of RR-DTC criteria, possibly because of a large overlap among patients fulfilling each criterion. However, differing definitions for RR-DTC may be equally valid because both lenvatinib and placebo arms exhibited similar PFS outcomes across groups.

    Original languageEnglish (US)
    Pages (from-to)1135-1141
    Number of pages7
    JournalThyroid
    Volume27
    Issue number9
    DOIs
    StatePublished - Sep 2017

    Keywords

    • Phase 3
    • lenvatinib
    • multitargeted kinase inhibitor
    • radioiodine therapy
    • thyroid cancer

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology

    Fingerprint Dive into the research topics of 'Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial'. Together they form a unique fingerprint.

  • Cite this