ASP8273 tolerability and antitumor activity in tyrosine kinase inhibitor-naïve Japanese patients with EGFR mutation-positive non-small-cell lung cancer

Koichi Azuma, Makoto Nishio, Hidetoshi Hayashi, Katsuyuki Kiura, Miyako Satouchi, Shunichi Sugawara, Toyoaki Hida, Yasuo Iwamoto, Akira Inoue, Koji Takeda, Satoshi Ikeda, Tomoki Nakagawa, Kentaro Takeda, Seitaro Asahina, Kanji Komatsu, Satoshi Morita, Masahiro Fukuoka, Kazuhiko Nakagawa, Koichi Azuma, Makoto Nishio, Hidetoshi Hayashi, Katsuyuki Kiura, Miyako Satouchi, Shunichi Sugawara, Toyoaki Hida, Yasuo Iwamoto, Akira Inoue, Koji Takeda, Satoshi Ikeda, Tomoki Nakagawa, Kentaro Takeda, Seitaro Asahina, Kanji Komatsu, Satoshi Morita, Masahiro Fukuoka, Kazuhiko Nakagawa

Abstract

Epidermal growth factor receptor (EGFR) activating mutations occur in approximately 50% of East Asian patients with non-small-cell lung cancer (NSCLC) and confer sensitivity to tyrosine kinase inhibitors (TKIs). ASP8273 is an irreversible EGFR-TKI, given orally, that inhibits EGFR activating mutations and has shown clinical activity in patients with EGFR mutation-positive NSCLC. Epidermal growth factor receptor-TKI-naïve Japanese adult patients (≥20 years) with NSCLC harboring EGFR mutations were enrolled in this open-label, single-arm, phase II study (ClinicalTrials.gov identifier NCT02500927). Patients received ASP8273 300 mg once daily until discontinuation criteria were met. The primary end-point was to determine the safety of ASP8273 300 mg; the secondary end-point was antitumor activity defined by RECIST version 1.1. Thirty-one patients (12 men and 19 women; median age, 64 years [range, 31-82 years]) with EGFR mutation-positive NSCLC were enrolled; as of 23 February 2016, 25 patients (81%) were still on study. Of the 31 patients, 27 (87%) had an exon 19 deletion (n = 13, 42%) or an L858R (n = 14, 45%) EGFR activating mutation, and two (7%) had an L861Q mutation. Five patients (16%) had other EGFR activating mutations, two had an activating mutation and the T790M resistance mutation. The most commonly reported treatment-emergent adverse event was diarrhea (n = 24, 77%). All patients had at least one post-baseline scan; one patient (3%) achieved a confirmed complete response, 13 (42%) had a confirmed partial response, and 15 (48%) had confirmed stable disease (disease control rate, 94% [n = 29/31]) per investigator assessment. Once-daily ASP8273 at 300 mg was generally well tolerated and showed antitumor activity in TKI-naïve Japanese patients with EGFR mutation-positive NSCLC.

Keywords: clinical trial; epidermal growth factor receptor; non-small-cell carcinoma; signal transduction inhibitors/kinase inhibitor; tyrosine kinase inhibitor.

© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Figures

Figure 1
Figure 1
Profile of phase II trial of ASP8273 tolerability and antitumor activity in tyrosine kinase inhibitor‐naïve Japanese patients with EGFR mutation‐positive non‐small‐cell lung cancer
Figure 2
Figure 2
Antitumor activity in tyrosine kinase inhibitor‐naïve Japanese patients with EGFR mutation‐positive non‐small‐cell lung cancer treated with ASP8273. A, Best percent change from baseline in target‐lesion size. B, Progression‐free survival of all subjects receiving ASP8273. C, Progression‐free survival of patients with exon 19 deletion (ex19del)‐positive mutation. D, Progression‐free survival of patients with L858R mutation

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