1033P - Subgroup analyses of a phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differen...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Thyroid Cancer
Translational Research
Presenter Rossella Elisei
Citation Annals of Oncology (2014) 25 (suppl_4): iv340-iv356. 10.1093/annonc/mdu340
Authors R. Elisei1, M.J. Schlumberger2, M. Tahara3, B. Robinson4, M. Brose5, C. Dutcus6, B.D.L. Heras7, J. Zhu8, M.A. Habra9, K. Newbold10, M. Shah11, A.O. Hoff12, A. Gianoukakis13, N. Kiyota14, M. Taylor15, S. Kim16, M.K. Krzyzanowska17, S. Sherman18, L.J. Wirth19
  • 1Endocrine Unit, Department Of Clinical And Experimental Medicine, University of Pisa, 56124 - Pisa/IT
  • 2Department Of Nuclear Medicine And Endocrine Oncology, Gustave Roussy and University Paris-Sud, Villejuif/FR
  • 3Department Of Head And Neck Medical Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 4Kolling Institute Of Medical Research, University of Sydney, NSW2006 - Sydney/AU
  • 5Department Of Otorhinolaryngology: Head And Neck Surgery, Abramson Cancer Center of the University of Pennsylvania, Philadelphia/US
  • 6Eisai, Eisai Inc., 07677 - Woodcliff Lake/US
  • 7Eisai, Eisai Ltd, England/GB
  • 8Eisai, Eisai Inc, Woodcliff Lake/US
  • 9Department Of Endocrine Neoplasia And Hormonal Disorders, The University of Texas M.D. Anderson Cancer Center, Houston/US
  • 10National Health Service Trust, Royal Marsden Hospital, London/GB
  • 11Departments Of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus/US
  • 12Department Of Endocrinology, Endocrine Oncology Unit, Instituto do Cancer do Estado de Sao Paulo, Universidade de Sao Paulo, 01308-050 - Sao Paulo/BR
  • 13Division Of Endocrinology And Metabolism, Harbor-UCLA Medical Center, Torrance/US
  • 14Department Of Medical Oncology And Hematology, Kobe University Hospital, JP-650-0017 - Kobe/JP
  • 15Knight Cancer Institute, Oregon Health and Science University, Portland/US
  • 16Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, KR-138-736 - Seoul/KR
  • 17Division Of Medical Oncology & Hematology, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 18Department Of Endocrine Neoplasia And Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Houston/US
  • 19Department Of Medicine, Massachusetts General Hospital, 02114 - Boston/US

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, PDGFRα, 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 < 0.0001). This subgroup analysis of SELECT examined efficacy outcomes based on patient demographics and baseline characteristics.

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.