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Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial.
Thyroid. 2017 09; 27(9):1135-1141.T

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.

Authors+Show Affiliations

1 Department of Medical Oncology and Hematology, Kobe University Hospital and Kobe University Hospital Cancer Center , Kobe, Japan .2 Kolling Institute of Medical Research, University of Sydney , New South Wales, Australia .3 Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center , Columbus, Ohio.4 Department of Endocrinology, Endocrine Oncology Unit, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo , São Paulo, Brazil .5 Knight Cancer Institute, Oregon Health and Science University , Portland, Oregon.6 Eisai, Inc. , Woodcliff Lake, New Jersey.6 Eisai, Inc. , Woodcliff Lake, New Jersey.7 Center for Thyroid Cancer, National Cancer Center , Goyang, South Korea .8 Asan Medical Center, University of Ulsan College of Medicine , Seoul, South Korea .9 Division of Head and Neck Medical Oncology, National Cancer Center Hospital East , Kashiwa, Japan .

Pub Type(s)

Clinical Trial
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28665259

Citation

Kiyota, Naomi, et al. "Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib By Radioiodine-Refractory Criteria in the SELECT Trial." Thyroid : Official Journal of the American Thyroid Association, vol. 27, no. 9, 2017, pp. 1135-1141.
Kiyota N, Robinson B, Shah M, et al. Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial. Thyroid. 2017;27(9):1135-1141.
Kiyota, N., Robinson, B., Shah, M., Hoff, A. O., Taylor, M. H., Li, D., Dutcus, C. E., Lee, E. K., Kim, S. B., & Tahara, M. (2017). Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial. Thyroid : Official Journal of the American Thyroid Association, 27(9), 1135-1141. https://doi.org/10.1089/thy.2016.0549
Kiyota N, et al. Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib By Radioiodine-Refractory Criteria in the SELECT Trial. Thyroid. 2017;27(9):1135-1141. PubMed PMID: 28665259.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial. AU - Kiyota,Naomi, AU - Robinson,Bruce, AU - Shah,Manisha, AU - Hoff,Ana O, AU - Taylor,Matthew H, AU - Li,Di, AU - Dutcus,Corina E, AU - Lee,Eun Kyung, AU - Kim,Sung-Bae, AU - Tahara,Makoto, Y1 - 2017/08/14/ PY - 2017/7/1/pubmed PY - 2018/5/23/medline PY - 2017/7/1/entrez KW - Phase 3 KW - lenvatinib KW - multitargeted kinase inhibitor KW - radioiodine therapy KW - thyroid cancer SP - 1135 EP - 1141 JF - Thyroid : official journal of the American Thyroid Association JO - Thyroid VL - 27 IS - 9 N2 - 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. SN - 1557-9077 UR - https://www.unboundmedicine.com/medline/citation/28665259/Defining_Radioiodine_Refractory_Differentiated_Thyroid_Cancer:_Efficacy_and_Safety_of_Lenvatinib_by_Radioiodine_Refractory_Criteria_in_the_SELECT_Trial_ L2 - https://www.liebertpub.com/doi/10.1089/thy.2016.0549?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -