Subgroup Analyses of a Phase 3, Multicenter, Double-Blind, Placebo-Controlled Trial of Lenvatinib (E7080) in Patients with 131I-Refractory Differentiated Thyroid Cancer

ABSTRACT Aim: In the phase 3 Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT), lenvatinib—an oral multikinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRa, RET, and KIT—prolonged progression-free survival (PFS) in patients (pts) with 131I-refractory differentiated thyroid cancer (RR-DTC) by 14.7 months vs placebo (hazard ratio [HR] 0.21; 95% confidence interval [CI] 0.14–0.31; P Methods: This multicenter, double-blind study randomized pts with RR-DTC 2:1 to lenvatinib or placebo (24mg/d; 28-d cycle). The primary endpoint was PFS. This analysis examines the efficacy outcomes of both predefined and exploratory subgroups. Results: The PFS advantage with lenvatinib vs placebo observed in the overall study population was maintained in all subgroups examined. Some subgroups, however, derived particular benefit from lenvatinib treatment. Among predefined subgroups, lenvatinib-treated pts with follicular thyroid cancer had a median PFS that had not yet been reached (HR 0.10; 95% CI 0.05–0.19) vs 16.4 months (HR 0.27; 95% CI 0.19–0.38) for papillary thyroid cancer; pts with baseline thyroid stimulating hormone (TSH) levels ≤0.5 µIU/mL had median PFS of 18.7 months (HR 0.20; 95% CI 0.14–0.27) vs pts with TSH >0.5–2.0 µIU/mL (median PFS 15.1 months; HR 0.35; 95% CI 0.09–1.39). In exploratory analyses, notable differences were observed between pts with progressive disease ≤3 months prior to randomization (median PFS 18.7 months; HR 0.19; 95% CI 0.14–0.27) vs progressive disease >3 months prior to randomization (median PFS 16.6 months; HR 0.44; 95% CI 0.20–0.96). Similarly, differences were observed between pts with renal impairment (median PFS 12.8 months; HR 0.85; 95% CI 0.31–2.31) and without (median PFS 20.2 months, HR 0.18; 95% CI 0.13–0.24) and between pts with hepatic impairment (median PFS 11.0 months; HR 0.18; 95% CI 0.06–0.57) and without (median PFS 18.7 months; HR 0.22; 95% CI 0.16–0.30). Conclusions: Lenvatinib PFS benefit was observed in all examined subgroups. Certain subgroups may exhibit a more profound response to lenvatinib treatment, which may warrant further investigation. Disclosure: M. Schlumberger: Advisory Role Expert Testimony: AstraZeneca, Bayer, Eisai, Genzyme-Sanofi.; onoraria: AstraZeneca, Bayer, Eisai, Genzyme-Sanofi, Sobi. Research Funding: AstraZeneca, Bayer, Eisai, Genzyme-Sanofi.; M. Tahara: Research Funding: Eisai, Boehringer-Ingelheim.; B. Robinson: Advisory Role: AstraZeneca, Bayer, Eisai.; M. Brose: Advisory Role: Eisai Research Funding: Eisai; C. Dutcus: Employee of Eisei Inc.; B.D.L. Heras: Employee of Eisai Ltd.; J. Zhu: Employee of Eisai Inc.; M. Shah: Advisory Role: Exelixis. Research Funding: Eisai, Exelixis, Bayer; A.O. Hoff: Research Funding: Eisai; A. Gianoukakis: Research Funding: Eisai; N. Kiyota: Research Funding: Eisai; S. Kim: Advisory Role: Novartis. Research Funding: Novartis; M.K. Krzyzanowska: Advisory Role: Bayer, Onxy. Research Funding: AstraZeneca, Exelixis, Eisai, Novartis; S. Sherman: Advisory Role: AstraZeneca, Amgen, Eisai, Exelixis, NovoNordisk, Eli Lilly. Research Funding: Amgen. All other authors have declared no conflicts of interest.