Department of Internal Medicine, Kurume University Hospital, Fukuoka, Japan.
Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Cancer Sci. 2018 Aug;109(8):2532-2538. doi: 10.1111/cas.13651. Epub 2018 Jun 29.
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.
表皮生长因子受体（EGFR）激活突变发生在大约 50%的东亚非小细胞肺癌（NSCLC）患者中，并对酪氨酸激酶抑制剂（TKI）敏感。ASP8273 是一种不可逆的 EGFR-TKI，口服给药，可抑制 EGFR 激活突变，并在 EGFR 突变阳性 NSCLC 患者中显示出临床活性。这项开放标签、单臂、II 期研究（ClinicalTrials.gov 标识符 NCT02500927）纳入了 EGFR 突变阳性 NSCLC 的日本成年初治（TKI 初治）患者（≥20 岁）。患者接受 ASP8273 300mg 每日一次，直到符合停药标准。主要终点是确定 ASP8273 300mg 的安全性；次要终点是根据 RECIST 版本 1.1 定义的抗肿瘤活性。31 名患者（12 名男性和 19 名女性；中位年龄 64 岁[范围 31-82 岁]）纳入 EGFR 突变阳性 NSCLC 患者；截至 2016 年 2 月 23 日，25 名患者（81%）仍在研究中。31 名患者中，27 名（87%）有 EGFR 激活突变，包括 19 名（61%）exon19 缺失（n=13，42%）和 8 名（26%）L858R（n=14，45%），2 名（7%）有 L861Q 突变。5 名患者（16%）有其他 EGFR 激活突变，2 名患者有激活突变和 T790M 耐药突变。最常见的治疗相关不良事件是腹泻（n=24，77%）。所有患者均至少有一次基线后扫描；1 名患者（3%）获得确认完全缓解，13 名患者（42%）获得确认部分缓解，15 名患者（48%）获得确认疾病稳定（疾病控制率为 94%[n=29/31]）。每日一次 ASP8273 300mg 耐受性良好，在 EGFR 突变阳性 NSCLC 的 TKI 初治日本患者中显示出抗肿瘤活性。
