TY - JOUR
T1 - Clinical activity of ASP8273 in Asian patients with non-small-cell lung cancer with EGFR activating and T790M mutations
AU - Murakami, Haruyasu
AU - Nokihara, Hiroshi
AU - Hayashi, Hidetoshi
AU - Seto, Takashi
AU - Park, Keunchil
AU - Azuma, Koichi
AU - Tsai, Chun Ming
AU - Yang, James Chih Hsin
AU - Nishio, Makoto
AU - Kim, Sang We
AU - Kiura, Katsuyuki
AU - Inoue, Akira
AU - Takeda, Koji
AU - Kang, Jin Hyoung
AU - Nakagawa, Tomoki
AU - Takeda, Kentaro
AU - Akazawa, Rio
AU - Kaneko, Yuichiro
AU - Shimazaki, Masashi
AU - Morita, Satoshi
AU - Fukuoka, Masahiro
AU - Nakagawa, Kazuhiko
N1 - Funding Information:
We would like to acknowledge all investigators, coordinators, and study site personnel, as well as patients and their families for their participation in this study. This research was sponsored by Astellas Pharma, Inc. (Tokyo, Japan). Financial support for the development of this manuscript, including writing and editorial assistance under the authors’ guidance, was provided by Melissa Creasey and Regina Switzer of SuccinctChoice Medical Communications (Chicago, IL, USA) and was funded by the study sponsor.
Publisher Copyright:
© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
KW - clinical trial
KW - epidermal growth factor receptor
KW - non-small-cell carcinoma
KW - signal transduction inhibitors/kinase inhibitor
KW - tyrosine kinase inhibitor
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U2 - 10.1111/cas.13724
DO - 10.1111/cas.13724
M3 - Article
C2 - 29972716
AN - SCOPUS:85052655193
SN - 1347-9032
VL - 109
SP - 2852
EP - 2862
JO - Cancer Science
JF - Cancer Science
IS - 9
ER -
