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

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.