1031P - Characterization of tumor size changes over time from the Phase 3 Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT)

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Thyroid Cancer
Imaging, Diagnosis and Staging
Presenter Bruce Robinson
Citation Annals of Oncology (2014) 25 (suppl_4): iv340-iv356. 10.1093/annonc/mdu340
Authors B. Robinson1, M.J. Schlumberger2, L.J. Wirth3, C. Dutcus4, B.D.L. Heras5, J. Zhu4, M. Taylor6, S.-. Kim7, M.K. Krzyzanowska8, J. Capdevila9, S. Sherman10, M. Tahara11
  • 1Kolling Institute Of Medical Research, University of Sydney, NSW2006 - Sydney/AU
  • 2Department Of Nuclear Medicine And Endocrine Oncology, Gustave Roussy and University Paris-Sud, Villejuif/FR
  • 3Department Of Medicine, Massachusetts General Hospital, 02114 - Boston/US
  • 4Eisai, Eisai Inc., Woodcliff Lake/US
  • 5Eisai, Eisai Ltd, England/GB
  • 6Knight Cancer Institute, Oregon Health and Science University, Portland/US
  • 7Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KP
  • 8Division Of Medical Oncology & Hematology, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 9Medical Oncology Department, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 10Department Of Endocrine Neoplasia And Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Houston/US
  • 11Department Of Head And Neck Medical Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP

Abstract

Aim

Lenvatinib—an oral, multityrosine kinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, 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 < 0.0001). Because the change in tumor volume was central to measuring patient response, this assessment was performed to further characterize the rate, magnitude, and duration of tumor size changes.

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 < 0.0001) using a random-effect model; the correlation between decrease in tumor size and treatment duration was 0.67.

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.