TY - JOUR
T1 - Defining Radioiodine-Refractory Differentiated Thyroid Cancer
T2 - 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
N1 - Funding Information:
The authors thank the patients, their families, the investigators, and the teams who participated in this trial. This study was funded by Eisai, Inc. Editorial assistance was provided by Oxford PharmaGenesis, Inc., and was funded by Eisai, Inc. This article was previously presented in part at the 18th European Cancer Congress (ECC) Annual Meeting, Vienna, Austria, September 25–29, 2015.
Funding Information:
N.K. received honoraria and grant support from Eisai, Inc., and received research funding from ONO, and Boehringer-Ingelheim Japan. B.R. served as an advisory board member for Eisai, Inc. M.S. received grants from Exelixis, Eisai, Inc., Bayer. A.O.H. received research funding from Eisai, Inc. M.H.T. received consulting/honoraria from Eisai, Inc., and ONYX. D.L. is an employee of Eisai, Inc. C.E.D. is an employee of Eisai, Inc. E.K.L. served as an advisory board member for Eisai, Inc. S.-B.K. received research funding from Novartis, Kyowha Kirin. M.T. received grants/fees from Ei-sai, Inc., Boehringher-Ingelheim, and honoraria from Merck-Serono, and BMS.
PY - 2017/9
Y1 - 2017/9
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.
AB - 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.
KW - Phase 3
KW - lenvatinib
KW - multitargeted kinase inhibitor
KW - radioiodine therapy
KW - thyroid cancer
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U2 - 10.1089/thy.2016.0549
DO - 10.1089/thy.2016.0549
M3 - Article
C2 - 28665259
AN - SCOPUS:85047293413
VL - 27
SP - 1135
EP - 1141
JO - Thyroid
JF - Thyroid
SN - 1050-7256
IS - 9
ER -