Characterization of Tumor Size Changes Over Time from the Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (Select)

Abstract

ABSTRACT Aim: Lenvatinib—an oral, multityrosine kinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRa, RET, and KIT—significantly improved the progression-free survival (PFS) of patients with 131I-refractory differentiated thyroid cancer (RR-DTC) when compared with placebo in a recent phase 3 clinical trial (median PFS: 18.3 months vs 3.6 months, respectively; P Methods: This analysis examined tumor burden and responses from the randomized, double-blind, multicenter Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT), in which patients with RR-DTC were randomized 2:1 to lenvatinib or placebo (24mg/d; 28-d cycle). Tumor assessments were performed by independent radiologic review using the Response Evaluation Criteria in Solid Tumors v1.1 at 8-week intervals. Results: Median tumor size at baseline for all patients receiving lenvatinib (n = 261) was 59.11 mm (sum of lesion diameters; range, 15.1 to 331.2). Median percent change in tumor size from baseline to nadir was -40.1% for all patients receiving lenvatinib (range, -100% to +65.6%). Based on median percent change, a tumor size reduction was experienced not only by responders (-52.1% [n = 169]; range, -100% to -30.3%) but also by nonresponders (-21.0% [n = 92]; range, -45.7% to +65.6%). The reduction in tumor size was most pronounced at the first assessment (∼25% at 8 weeks postrandomization); thereafter, the rate of change was slower but remained continuous. Patients receiving ≥1 year of treatment had an initial tumor shrinkage rate of 27.4% in the first 8 weeks; after 8 weeks, tumor sizes reduced at similar rates for all patients. The change in tumor size over time was -1.3 % per month (P Conclusions: For patients with RR-DTC, the change in tumor size was characterized by 2 phases: an initial, rapid decline, followed by slower, continuous shrinkage. The magnitude of this decrease was associated with treatment duration. These findings offer important clinical insight for lenvatinib use in RR-DTC. Disclosure: B. Robinson: Advisory Role: AstraZeneca, Bayer, Eisai; M. Schlumberger: Advisory Role/Expert Testimony: AstraZeneca, Bayer, Eisai, Genzyme-Sanofi. Honoraria: AstraZeneca, Bayer, Eisai, Genzyme-Sanofi, Sobi. Research Funding: AstraZeneca, Bayer, Eisai, Genzyme-Sanofi; C. Dutcus: Employee of Eisai Inc.; B.D.L. Heras: Employee of Eisai Ltd; J. Zhu: Employee of Eisai Inc.; 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; M. Tahara: Research Funding: Eisai, Boehringer-Ingelheim. All other authors have declared no conflicts of interest.