Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine‐refractory differentiated thyroid cancer

Cancer Science

Naomi Kiyota¹⁰  Martin Schlumberger³  Kei Muro⁸  Yuichi Ando¹³  Shunji Takahashi¹  Yasukazu Kawai⁹  Lori Wirth¹²  Bruce Robinson¹¹  Steven Sherman⁶  Takuya Suzuki^7,10  Katsuki Fujino^4,10  Anubha Gupta^5,10  Seiichi Hayato^2,10 

[1] Department of Medical Oncology, Cancer Institute Hospital of JFCR, Tokyo, Japan;Clinical Pharmacology, Eisai Co., Ltd, Tokyo, Japan;Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris-Sud, Villejuif, France;Japan Biostatistics, Eisai Co., Ltd, Tokyo, Japan;Clinical Pharmacology, Eisai Ltd., Hatfield, UK;Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA;Oncology Clinical Development, Eisai Co., Ltd, Tokyo, Japan;Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan;Department of Hematology and Oncology, Fukui Prefectural Hospital, Fukui, Japan;Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan;Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia;Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA;Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan

关键词: Japanese patients;    lenvatinib;    progression‐free survival;    thyroid cancer;    treatment efficacy;   

DOI  :  10.1111/cas.12826

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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