A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT).

Head and Neck Cancer
Session Type and Session Title: 
Oral Abstract Session, Head and Neck Cancer
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr LBA6008)
Martin Schlumberger, Makoto Tahara, Lori J. Wirth, Bruce Robinson, Marcia S. Brose, Rossella Elisei, Corina E. Dutcus, Begoña de las Heras, Junming Zhu, Mouhammed Amir Habra, Kate Newbold, Manisha H. Shah, Ana O. Hoff, Andrew G Gianoukakis, Naomi Kiyota, Matthew Hiram Taylor, Sung-Bae Kim, Monika K Krzyzanowska, Steven I. Sherman; Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris-Sud, Villejuif, France; Division of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Department of Medicine, Massachusetts General Hospital, Boston, MA; Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia; Department of Otorhinolaryngology: Head and Neck Surgery, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; Department of Endocrinology, University of Pisa, Pisa, Italy; Eisai, Woodcliff Lake, NJ; Eisai, Hatfield, Hertfordshire, United Kingdom; Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; Royal Marsden Hospital National Health Service Trust, London, United Kingdom; Departments of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Instituto do Cancer do Estado de Sao Paulo, Universidade de Sao Paulo, São Paulo, Brazil; Division of Endocrinology and Metabolism, Harbor-UCLA Medical Center, Torrance, CA; Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan; Knight Cancer Institute, Oregon Health and Science University, Portland, OR; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Princess Margaret Cancer Centre, Toronto, ON, Canada

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Abstract Disclosures


Background: Lenvatinib (LEN) is an oral tyrosine kinase inhibitor of the VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT signaling networks. Based on efficacy results of the phase 2 study of patients (pts) with 131I-refractory differentiated thyroid cancer (RR-DTC), this phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) was developed. Methods: This randomized, double-blind, placebo (PBO)-controlled study enrolled pts with RR-DTC with documented disease progression within 13 months (mo). Pts were stratified by age (≤65, >65 years), region and ≤1 prior VEGFR-targeted therapies and randomized 2:1 to LEN or PBO (24mg/d, 28-d cycle). Upon progression, pts receiving PBO could crossover to open-label LEN. The primary endpoint was PFS assessed by Independent Radiologic Review; secondary endpoints included overall response rate (ORR; complete response [CR] + PR), overall survival (OS) and safety. Results: 392 pts (63.0 years median age; 51.0% male) were randomized. Pts on LEN had a significantly prolonged PFS vs PBO (hazard ratio 0.21, 95% confidence interval [CI] 0.14–0.31; P <.0001); median PFS was LEN: 18.3 mo (95% CI 15.1–not evaluable), PBO: 3.6 mo (95% CI 2.2–3.7). A LEN PFS benefit was observed in all predefined subgroups; median LEN PFS for pts with prior vs no prior VEGF-therapy was 15.1 mo (n=66) and 18.7 mo (n=195), respectively. Rates (n) of CRs were LEN: 1.5% (4), PBO: 0; PRs were LEN: 63.2% (165), PBO: 1.5% (2).Median exposure duration was LEN: 13.8 mo, PBO: 3.9 mo; median time to LEN response was 2.0 mo. Median OS has not been reached; deaths per arm were LEN: 71 (27.2%), PBO: 47 (35.9%). The 5 most common LEN treatment-related adverse events (TRAEs; any grade) were hypertension (68%), diarrhea (59%), appetite decreased (50%), weight loss (46%), nausea (41%). LEN grade ≥3 TRAEs (≥5%) were hypertension (42%), proteinuria (10%), weight loss (10%), diarrhea (8%), appetite decreased (5%). The dose was reduced in 78.5% of pts and discontinued due to adverse events (AEs) in 14.2% of pts. Conclusions: LEN significantly improved PFS compared with PBO in pts with progressive RR-DTC. There were no unexpected toxicities and AEs were manageable. Clinical trial information: NCT01321554.