一项II期研究（WJOG12819L）旨在评估奥西替尼在EGFR突变阳性非小细胞肺癌患者中的疗效，这些患者在使用第一代或第二代EGFR酪氨酸激酶抑制剂和铂类化疗之后，其全身性疾病（T790M阴性）进展。
A phase II study (WJOG12819L) to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy.
发表日期：2023 Mar
作者：
Masayuki Takeda, Mototsugu Shimokawa, Atsushi Nakamura, Kaname Nosaki, Yasutaka Watanabe, Terufumi Kato, Daisuke Hayakawa, Hiroshi Tanaka, Toshiaki Takahashi, Masahide Oki, Motoko Tachihara, Daichi Fujimoto, Hidetoshi Hayashi, Kakuhiro Yamaguchi, Shoichiro Yamamoto, Eiji Iwama, Koichi Azuma, Kazuo Hasegawa, Nobuyuki Yamamoto, Kazuhiko Nakagawa
来源：
LUNG CANCER
摘要：
Osimertinib是第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），已成为EGFR突变阳性非小细胞肺癌（NSCLC）化疗前患者的标准治疗选择。然而，对于那些先前接受第一代或第二代EGFR TKI治疗的患者，只有大约一半有资格接受osimertinib治疗，因为其作为第二线治疗及以上的适应症仅限于EGFR基因中T790M耐药突变阳性的转移性NSCLC。本研究是应日本肺癌患者专业网络的请求而发起的。我们进行了一项II期研究，评估osimertinib在经一代或二代EGFR TKI和基于铂的化疗治疗后仍有系统性疾病（T790M阴性）的EGFR突变阳性NSCLC患者中的疗效。主要终点是响应率（由中央成像评估员评估）。从2020年8月至2021年2月，来自15个机构的55名患者参加了这项研究。主要分析的总体响应率为16名患者（29.1％；95％CI，17.6-42.9），超过了分析所需的阈值响应率。16名患者（29.1％）出现稳定疾病，18名（32.7％）出现进展性疾病。无进展生存期（PFS）的中位数为4.07个月（95％CI 2.10-4.30），12个月PFS率为17.3％。osimertinib对进展性EGFR T790M阴性疾病表现出适度的抗肿瘤活性。版权所有©2023 The Author（s）。Elsevier B.V.发表。保留所有权利。
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is an established standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). However, of such patients who have received prior treatment with a first- or second-generation EGFR TKI, only approximately half are eligible for osimertinib therapy because its indication as second-line treatment and beyond is limited to metastatic NSCLC that is positive for the T790M resistance mutation of the EGFR gene. This study was initiated at the request of a dedicated network for patients with lung cancer in Japan.We conducted a phase II study to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy. The primary end point was response rate (assessed by a central imaging reviewer).From August 2020 to February 2021, 55 patients from 15 institutions were enrolled in the study. The overall response for primary analysis was achieved in 16 patients (29.1 %; 95 % CI, 17.6-42.9), which exceeded the threshold response rate necessary for analysis. Stable disease was found in 16 patients (29.1 %), and progressive disease, in 18 (32.7 %). The median length of progression-free survival (PFS) was 4.07 months (95 % CI 2.10-4.30), and the rate of 12-month PFS was 17.3 %.Osimertinib demonstrated modest antitumor activity against progressive EGFR T790M-negative disease.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.