神戸大学附属図書館デジタルアーカイブ
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https://hdl.handle.net/20.500.14094/90005476
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2024-05-04
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90005476 (fulltext)
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メタデータID
90005476
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open access
出版タイプ
Version of Record
タイトル
Exploratory analysis of biomarkers associated with clinical outcomes from the study of lenvatinib in differentiated cancer of the thyroid
著者
Tahara, Makoto ; Schlumberger, Martin ; Elisei, Rossella ; Habra, Mouhammed Amir ; Kiyota, Naomi ; Paschke, Ralf ; Dutcus, Corina E. ; Hihara, Taro ; McGrath, Shannon ; Matijevic, Mark ; Kadowaki, Tadashi ; Funahashi, Yasuhiro ; Sherman, Steven I.
著者名
Tahara, Makoto
著者名
Schlumberger, Martin
著者名
Elisei, Rossella
著者名
Habra, Mouhammed Amir
著者ID
A1407
研究者ID
1000040515037
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=5fd898ae58a689e3520e17560c007669
著者名
Kiyota, Naomi
清田, 尚臣
キヨタ, ナオミ
所属機関名
医学部附属病院
著者名
Paschke, Ralf
著者名
Dutcus, Corina E.
著者名
Hihara, Taro
著者名
McGrath, Shannon
著者名
Matijevic, Mark
著者名
Kadowaki, Tadashi
著者名
Funahashi, Yasuhiro
著者名
Sherman, Steven I.
収録物名
European Journal of Cancer
巻(号)
75
ページ
213-221
出版者
Elsevier
刊行日
2017-04
公開日
2018-12-20
抄録
Background: Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in the phase III Study of (E7080) LEnvatinib in differentiated Cancer of the Thyroid (SELECT) of patients with radioiodine-refractory differentiated thyroid cancer. This exploratory analysis investigated potential predictive biomarkers of lenvatinib efficacy and target engagement. Patients and methods: Circulating cytokine/angiogenic factors (CAFs) in blood samples collected at baseline and throughout treatment were analysed from patients randomised to receive lenvatinib or placebo from August 5, 2011 to October 4, 2012. For CAF biomarker analyses, patients were dichotomised by baseline levels. Tumour tissues were analysed for BRAF and NRASIKRASIHRAS mutations. Results: Tumours and CAFs were analysed from 183/392 (47%) and 387/392 (99%) patients, respectively. Lenvatinib PFS benefit was maintained in all assessments. For lenvatinibtreated patients, interaction-term analyses revealed that low baseline Ang2 level was predictive of tumour shrinkage (P-interaction = 0.016) and PFS (P-interaction = 0.018). Vascular endothelial growth factor and fibroblast growth factor 23 (FGF23) were significantly upregulated with lenvatinib, and FGF23 upregulation on cycle 1/day 15 was associated with longer PFS. In mutation analyses, no significant differences in clinical outcomes were observed. BRAF(WT) may be a negative prognostic factor for PFS in placebo-treated patients with papillary thyroid cancer (P = 0.019). Conclusion: The lenvatinib PFS benefit was maintained regardless of baseline CAF or BRAF/RAS status. Baseline Ang2 was predictive of PFS in a subgroup of lenvatinib-treated patients, indicating that Ang2 may be predictive of lenvatinib sensitivity. BRAF(WT) may be a poor prognostic factor in patients with radioiodine-refractory papillary thyroid cancer. Improved PFS associated with upregulated FGF23 suggests that lenvatinib-induced FGF receptor inhibition contributes to lenvatinib efficacy.
キーワード
Lenvatinib
Biomarkers
Thyroid cancer
Tyrosine kinase inhibitor
Phase 3
Clinical trial
カテゴリ
医学部附属病院
学術雑誌論文
権利
© 2017 The Authors. Published by Elsevier Ltd.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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資源タイプ
journal article
言語
English (英語)
ISSN
0959-8049
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eISSN
1879-0852
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関連情報
DOI
https://doi.org/10.1016/j.ejca.2017.01.013
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