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ID 114898
Author
Murakami, Haruyasu Shizuoka Cancer Center
Hayashi, Hidetoshi Kindai University
Seto, Takashi National Kyushu Cancer Center
Park, Keunchil Samsung Medical Center
Azuma, Koichi Kurume University
Tsai, Chun-Ming Taipei Veterans General Hospital
Yang, James Chih-Hsin National Taiwan University
Nishio, Makoto Japanese Foundation for Cancer Research
Kim, Sang-We University of Ulsan
Kiura, Katsuyuki Okayama University
Inoue, Akira Tohoku University
Takeda, Koji Osaka City General Hospital
Kang, Jin-Hyoung The Catholic University of Korea
Nakagawa, Tomoki Astellas Pharma
Takeda, Kentaro Astellas Pharma
Akazawa, Rio Astellas Pharma
Kaneko, Yuichiro Astellas Pharma
Shimazaki, Masashi Astellas Pharma
Morita, Satoshi Kyoto University
Fukuoka, Masahiro Izumi General Hospital
Nakagawa, Kazuhiko Kindai University
Keywords
clinical trial
epidermal growth factor receptor
non-small-cell carcinoma
signal transduction inhibitors/kinase inhibitor
tyrosine kinase inhibitor
Content Type
Journal Article
Description
Epidermal growth factor receptor (EGFR)‐activating mutations confer sensitivity to tyrosine kinase inhibitor (TKI) treatment for non‐small‐cell lung cancer (NSCLC). ASP8273 is a highly specific, irreversible, once‐daily, oral, EGFR TKI that inhibits both activating and resistance mutations. This ASP8273 dose‐escalation/dose‐expansion study (NCT02192697) was undertaken in two phases. In phase I, Japanese patients (aged ≥20 years) with NSCLC previously treated with ≥1 EGFR TKI received escalating ASP8273 doses (25‐600 mg) to assess safety/tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) by the Bayesian Continual Reassessment Method. In phase II, adult patients with T790M‐positive NSCLC in Japan, Korea, and Taiwan received ASP8273 at RP2D to further assess safety/tolerability and determine antitumor activity, which was evaluated according to Simon's two‐stage design (threshold response = 30%, expected response = 50%, α = 0.05, β = 0.1). Overall, 121 (n = 45 [33W/12M] phase I, n = 76 [48W/28M]) phase 2) patients received ≥1 dose of ASP8273. In phase I, RP2D and MTD were established as 300 and 400 mg, respectively. As 27 of the 63 patients treated with ASP8273 300 mg achieved a clinical response, ASP8273 was determined to have antitumor activity. The overall response rate at week 24 in all patients was 42% (n = 32/76; 95% confidence interval, 30.9‐54.0). Median duration of progression‐free survival was 8.1 months (95% confidence interval, 5.6, upper bound not reached). The most commonly reported treatment‐related adverse event in phase II was diarrhea (57%, n = 43/76). ASP8273 300 mg was generally well tolerated and showed antitumor activity in Asian patients with both EGFR‐activating and T790M mutations.
Journal Title
Cancer Science
ISSN
13497006
Publisher
Japanese Cancer Association|John Wiley & Sons
Volume
109
Issue
9
Start Page
2852
End Page
2862
Published Date
2018-07-04
Remark
所属英表記誤記あり (誤)Hizuoka Cancer Center→(正)Shizuoka Cancer Center
Rights
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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language
eng
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departments
University Hospital