title: Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer.
abstract: Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. This subanalysis evaluated the efficacy and safety of lenvatinib in Japanese patients who participated in SELECT. Outcomes for Japanese patients (lenvatinib, n = 30; placebo, n = 10) were assessed in relationship to the SELECT population (lenvatinib, n = 261; placebo, n = 131). The primary endpoint was PFS; secondary endpoints included overall survival, overall response rate, and safety. Lenvatinib PFS benefit was shown in Japanese patients (median PFS: lenvatinib, 16.5 months; placebo, 3.7 months), although significance was not reached, presumably due to sample size (hazard ratio, 0.39; 95% confidence interval, 0.10-1.57; P = 0.067). Overall response rates were 63.3% and 0% for lenvatinib and placebo, respectively. No significant difference was found in overall survival. The lenvatinib safety profile was similar between the Japanese and overall SELECT population, except for higher incidences of hypertension (any grade: Japanese, 87%; overall, 68%; grade ≥3: Japanese, 80%; overall, 42%), palmar-plantar erythrodysesthesia syndrome (any grade: Japanese, 70%; overall, 32%; grade ≥3: Japanese, 3%; overall, 3%), and proteinuria (any grade: Japanese, 63%; overall, 31%; grade ≥3: Japanese, 20%; overall, 10%). Japanese patients had more dose reductions (Japanese, 90%; overall, 67.8%), but fewer discontinuations due to adverse events (Japanese, 3.3%; overall, 14.2%). There was no difference in lenvatinib exposure between the Japanese and overall SELECT populations after adjusting for body weight. In Japanese patients with radioiodine-refractory differentiated thyroid cancer, lenvatinib showed similar clinical outcomes to the overall SELECT population. Some differences in adverse event frequencies and dose modifications were observed. Clinical trial registration no.: NCT01321554.
authors.affiliation: Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kiyota
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris-Sud, Villejuif, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
authors.affiliation: Department of Medical Oncology, Cancer Institute Hospital of JFCR, Tokyo, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Hematology and Oncology, Fukui Prefectural Hospital, Fukui, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Kawai
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Wirth
authors.affiliation: Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Robinson
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Sherman
authors.affiliation: Oncology Clinical Development, Eisai Co., Ltd, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Japan Biostatistics, Eisai Co., Ltd, Tokyo, Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Fujino
authors.affiliation: Clinical Pharmacology, Eisai Ltd., Hatfield, UK.
authors.forename: Anubha
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Clinical Pharmacology, Eisai Co., Ltd, Tokyo, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hayato
authors.affiliation: Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tahara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010671:Phenylurea Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011804:Quinolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D010671:Phenylurea Compounds; D011804:Quinolines; C531958:lenvatinib
keywords: Japanese patients; lenvatinib; progression-free survival; thyroid cancer; treatment efficacy