Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer
Open Access
- 17 October 2016
- journal article
- research article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 101 (11), 4103-4109
- https://doi.org/10.1210/jc.2015-3989
Abstract
Context: Lenvatinib improved the progression-free survival (PFS) and overall response rate of patients with radioiodine-refractory differentiated thyroid cancer vs placebo in the Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT). Objective: The objective of the study was to characterize tumor size changes with lenvatinib treatment. Design: SELECT was a phase 3, randomized, double-blind, multicenter study. Setting: In this clinical trial, tumor assessments of lenvatinib (n = 261) and placebo-treated (n = 131) patients were performed by independent radiological review per Response Evaluation Criteria in Solid Tumors version, 1.1 at 8-week intervals. Patients: Patients with complete or partial response were defined as responders to lenvatinib (n = 169). Of the 92 nonresponders, 76 had at least one postbaseline tumor assessment and were included in this analysis. Interventions: Lenvatinib (24 mg once daily) or placebo in 28-day cycles until unacceptable toxicity, disease progression, or death. Main Outcome Measures: This was an exploratory analysis of key end points from SELECT, including PFS, overall response rate, and tumor reduction. Results: The median maximum percentage change in tumor size was −42.9% for patients receiving lenvatinib (responders, −51.9%; nonresponders, −20.2%). Tumor size reduction was most pronounced at first assessment (median, −24.7% at 8 wk after randomization); thereafter, the rate of change was slower but continuous (−1.3% per mo). In a multivariate model, percentage change in tumor size at the first assessment was a marginally significant positive predictor for PFS (P = .06). Conclusions: The change in tumor size conferred by lenvatinib was characterized by two phases: an initial, rapid decline, followed by slower, continuous shrinkage.Keywords
This publication has 12 references indexed in Scilit:
- Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level AnalysesJournal of Clinical Oncology, 2015
- Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid CancerThe New England Journal of Medicine, 2015
- Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical CharacterizationACS Medicinal Chemistry Letters, 2014
- Efficacy and Tolerability of Different Starting Doses of Sorafenib in Patients With Differentiated Thyroid CancerThe Oncologist, 2014
- Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor modelsCancer Letters, 2013
- Change in Tumor Size by RECIST Correlates Linearly With Overall Survival in Phase I Oncology StudiesJournal of Clinical Oncology, 2012
- Modes of resistance to anti-angiogenic therapyNature Reviews Cancer, 2008
- E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibitionInternational Journal of Cancer, 2007
- Fibroblast Growth Factor Receptors as Molecular Targets in Thyroid CarcinomaEndocrinology, 2005
- RET/PTC Rearrangement in Thyroid TumorsEndocrine Pathology, 2002